Valproate

Short description: Medication used for epilepsy, bipolar disorder and migraine

Valproate
INN: valproic acid

Clinical data
Trade names| Depakote, Epilim, Convulex, others
Other names| Valproic acid; Sodium valproate (sodium); Valproate semisodium (semisodium); 2-Propylvaleric acid
AHFS/Drugs.com| Monograph
MedlinePlus| a682412
License data|

* US DailyMed: Valproic_acid
* US FDA: Valproic acid

Pregnancy
category|

* AU: D

Routes of
administration| By mouth, intravenous
ATC code|

* N03AG01 (WHO)

Legal status
Legal status|

* AU: S4 (Prescription only)
* CA: ℞-only
* UK: POM (Prescription only)
* US: ℞-only

Pharmacokinetic data
Bioavailability| Rapid absorption
Protein binding| 80–90%[1]
Metabolism| Liver—glucuronide conjugation 30–50%, mitochondrial β-oxidation over 40%
Elimination half-life| 9–16 hours[1]
Excretion| Urine (30–50%)[1]
Identifiers

IUPAC name

* 2-propylpentanoic acid

CAS Number|

* 99-66-1 Y

PubChem CID|

* 3121

IUPHAR/BPS|

* 7009

DrugBank|

* DB00313 Y

ChemSpider|

* 3009 Y

UNII|

* 614OI1Z5WI

KEGG|

* D00399 Y

ChEBI|

* CHEBI:39867 Y

ChEMBL|

* ChEMBL109 Y

NIAID ChemDB|

* 057177

Chemical and physical data
Formula| C8H16O2
Molar mass| 144.214 g·mol−1
3D model (JSmol)|

* Interactive image

SMILES

* O=C(O)C(CCC)CCC

InChI

* InChI=1S/C8H16O2/c1-3-5-7(6-4-2)8(9)10/h7H,3-6H2,1-2H3,(H,9,10) Y

* Key:NIJJYAXOARWZEE-UHFFFAOYSA-N Y

(verify)

Valproate (VPA) and its valproic acid, sodium valproate, and valproate semisodium forms are medications primarily used to treat epilepsy and bipolar disorder and prevent migraine headaches.[2] They are useful for the prevention of seizures in those with absence seizures, partial seizures, and generalized seizures.[2] They can be given intravenously or by mouth, and the tablet forms exist in both long- and short-acting formulations.[2]

Common side effects of valproate include nausea, vomiting, sleepiness, and dry mouth.[2] Serious side effects can include liver failure, and regular monitoring of liver function tests is therefore recommended.[2] Other serious risks include pancreatitis and an increased suicide risk.[2] Valproate is known to cause serious abnormalities in babies if taken during pregnancy,[2][3] and as such it is not typically recommended for women of childbearing age who have migraines.[2]

Valproate's precise mechanism of action is unclear.[2][4] Proposed mechanisms include affecting GABA levels, blocking voltage-gated sodium channels, and inhibiting histone deacetylases.[5][6] Valproic acid is a branched short-chain fatty acid (SCFA) made from valeric acid.[5]

Valproate was first made in 1881 and came into medical use in 1962.[7] It is on the World Health Organization's List of Essential Medicines[8] and is available as a generic medication.[2] In 2019, it was the 114th most commonly prescribed medication in the United States, with more than 5 million prescriptions.[9][10]

## Contents

* 1 Terminology
* 2 Medical uses
* 2.1 Epilepsy
* 2.2 Mental illness
* 2.2.1 Bipolar disorder
* 2.2.2 Schizophrenia
* 2.2.3 Dopamine dysregulation syndrome
* 2.3 Migraines
* 2.4 Other
* 3 Contraindications
* 4 Adverse effects
* 4.1 Pregnancy
* 4.2 Elderly
* 5 Overdose and toxicity
* 6 Interactions
* 7 Pharmacology
* 7.1 Pharmacodynamics
* 7.1.1 Endocrine actions
* 7.2 Pharmacokinetics
* 8 Chemistry
* 9 History
* 10 Society and culture
* 10.1 Approval status
* 10.2 Off-label uses
* 10.3 Formulations
* 10.3.1 Brand names of valproic acid
* 10.3.2 Brand names of sodium valproate
* 10.3.2.1 Portugal
* 10.3.2.2 United States
* 10.3.2.3 Australia
* 10.3.2.4 New Zealand
* 10.3.2.5 UK
* 10.3.2.5.1 UK only
* 10.3.2.6 Germany, Switzerland, Norway, Finland, Sweden
* 10.3.2.7 South Africa
* 10.3.2.8 Malaysia
* 10.3.2.9 Romania
* 10.3.2.10 Canada
* 10.3.2.11 Japan
* 10.3.2.12 Europe
* 10.3.2.13 Taiwan
* 10.3.2.14 Iran
* 10.3.2.15 Israel
* 10.3.2.16 India, Russia and CIS countries
* 10.3.3 Brand names of valproate semisodium
* 11 References
* 12 External links

## Terminology

Valproic acid (VPA) is an organic weak acid. The conjugate base is valproate. The sodium salt of the acid is sodium valproate and a coordination complex of the two is known as valproate semisodium.[11]

## Medical uses

It is used primarily to treat epilepsy and bipolar disorder. It is also used to prevent migraine headaches.[12]

### Epilepsy

Valproate has a broad spectrum of anticonvulsant activity, although it is primarily used as a first-line treatment for tonic–clonic seizures, absence seizures and myoclonic seizures and as a second-line treatment for partial seizures and infantile spasms.[12][13] It has also been successfully given intravenously to treat status epilepticus.[14][15]

### Mental illness

#### Bipolar disorder

Valproate products are also used to treat manic or mixed episodes of bipolar disorder.[16][17]

#### Schizophrenia

A 2016 systematic review compared the efficacy of valproate as an add-on for people with schizophrenia:[18]

There is limited evidence that adding valproate to antipsychotics may be effective for overall response and also for specific symptoms, especially in terms of excitement and aggression. Valproate was associated with a number of adverse events among which sedation and dizziness appeared more frequently than in the control groups.[18]

| Outcome  | Findings in words  | Findings in numbers  | Quality of evidence

|
|
|

Global outcome
Clinically significant response | When added to antipsychotic drugs valproate probably increases the chance of improvement. Data are based on moderate quality evidence.  | RR 1.31 (1.16 to 1.47) | Moderate
Leaving the study early for any reason | Valproate in combination with antipsychotics may slightly reduce the chance of leaving the study early, but the difference between the two treatments is not clear. Data supporting this finding are based on moderate quality evidence.  | RR 0.76 (0.47 to 1.24) | Moderate
Use of additional medication for sedation | The combination of valproate and antipsychotic drugs may increase the chance of being given additional sedating medication, but, at present it is not possible to be confident about the difference between the two treatments and data supporting this finding are very limited.  | RR 3.65 (0.11 to 122.31) | Very low
Mental state
Average score (PANSS total, high = poor) | On average, people receiving the valproate combination scored lower (better) than people treated with antipsychotics in combination with placebo or antipsychotic drugs alone. There was a clear difference between the groups, but the meaning of this in day-to-day care is unclear. | MD 5.85 lower (7.8 lower to 3.91 lower) | Moderate
Adverse events
Abnormal liver function (blood test changes)* | Adding valproate to antipsychotic drug treatment does not clearly cause liver problems. Data supporting this finding are based on moderate quality evidence.  | RR 1.26 (0.72 to 2.22) | Moderate
Nausea | Adding valproate to antipsychotic drugs probably causes little or no increase to the chance of feeling sick, but the difference between the two treatments is not clear. Data supporting this finding are based on moderate quality evidence.  | RR 1.22 (0.80 to 1.86) | Moderate
Missing outcomes and notes
| Quality of life outcomes were not reported in the included studies.
*Increase in alanine transaminase/gamma-glutamyl transpeptidase |  |

#### Dopamine dysregulation syndrome

Based upon five case reports, valproic acid may have efficacy in controlling the symptoms of the dopamine dysregulation syndrome that arise from the treatment of Parkinson's disease with levodopa.[19][20][21]

### Migraines

Valproate is also used to prevent migraine headaches. Because this medication can be potentially harmful to the fetus, valproate should be considered for those able to become pregnant only after the risks have been discussed.[22]

### Other

The medication has been tested in the treatment of AIDS and cancer, owing to its histone-deacetylase-inhibiting effects.[23]

## Contraindications

Contraindications include:

* Pre-existing acute or chronic liver dysfunction or family history of severe liver inflammation (hepatitis), particularly medicine related.[24]
* Known hypersensitivity to valproate or any of the ingredients used in the preparation[24]
* Urea cycle disorders[24]
* Hepatic porphyria[24]
* Hepatotoxicity[24]
* Mitochondrial disease[24]
* Pancreatitis[24]
* Porphyria[25]

## Adverse effects

Most common adverse effects include:[22]

* Nausea (22%)
* Drowsiness (19%)
* Dizziness (12%)
* Vomiting (12%)
* Weakness (10%)

Serious adverse effects include:[22]

* Bleeding
* Low blood platelets
* Encephalopathy
* Suicidal behavior and thoughts
* Low body temperature

Valproic acid has a black box warning for hepatotoxicity, pancreatitis, and fetal abnormalities.[22]

There is evidence that valproic acid may cause premature growth plate ossification in children and adolescents, resulting in decreased height.[26][27][28][29] Valproic acid can also cause mydriasis, a dilation of the pupils.[30] There is evidence that shows valproic acid may increase the chance of polycystic ovary syndrome (PCOS) in women with epilepsy or bipolar disorder. Studies have shown this risk of PCOS is higher in women with epilepsy compared to those with bipolar disorder.[31] Weight gain is also possible.[32]

### Pregnancy

Valproate causes birth defects;[33] exposure during pregnancy is associated with about three times as many major abnormalities as usual, mainly spina bifida with the risks being related to the strength of medication used and use of more than one drug.[34][35] More rarely, with several other defects, including a "valproate syndrome".[36] Characteristics of this valproate syndrome include facial features that tend to evolve with age, including a triangle-shaped forehead, tall forehead with bifrontal narrowing, epicanthic folds, medial deficiency of eyebrows, flat nasal bridge, broad nasal root, anteverted nares, shallow philtrum, long upper lip and thin vermillion borders, thick lower lip and small downturned mouth.[37] While developmental delay is usually associated with altered physical characteristics (dysmorphic features), this is not always the case.[38]

Children of mothers taking valproate during pregnancy are at risk for lower IQs.[39][40][41] Maternal valproate use during pregnancy increased the probability of autism in the offspring compared to mothers not taking valproate from 1.5% to 4.4%.[42] A 2005 study found rates of autism among children exposed to sodium valproate before birth in the cohort studied were 8.9%.[43] The normal incidence for autism in the general population is estimated at less than one percent.[44] A 2009 study found that the 3-year-old children of pregnant women taking valproate had an IQ nine points lower than that of a well-matched control group. However, further research in older children and adults is needed.[45][46][47]

Sodium valproate has been associated with paroxysmal tonic upgaze of childhood, also known as Ouvrier–Billson syndrome, from childhood or fetal exposure. This condition resolved after discontinuing valproate therapy.[48][49]

Women who intend to become pregnant should switch to a different medication if possible or decrease their dose of valproate.[50] Women who become pregnant while taking valproate should be warned that it causes birth defects and cognitive impairment in the newborn, especially at high doses (although valproate is sometimes the only drug that can control seizures, and seizures in pregnancy could have worse outcomes for the fetus than exposure to valproate). Studies have shown that taking folic acid supplements can reduce the risk of congenital neural tube defects.[22] The use of valproate for migraine or bipolar disorder during pregnancy is contraindicated in the European Union, and the medicines are not recommended for epilepsy during pregnancy unless there is no other effective treatment available.[51]

### Elderly

Valproate in elderly people with dementia caused increased sleepiness. More people stopped the medication for this reason. Additional side effects of weight loss and decreased food intake were also associated with one-half of people who become sleepy.[22]

## Overdose and toxicity

Therapeutic range of valproic acid  Form | Lower limit | Upper limit | Unit

|
|
|

Total (including
protein bound)  | 50[52] | 125[52] | µg/mL or mg/l
350[53] | 700[53] | μmol/L
Free  | 6[52] | 22[52] | µg/mL or mg/l
35[53] | 70[53] | μmol/L

Excessive amounts of valproic acid can result in sleepiness, tremor, stupor, respiratory depression, coma, metabolic acidosis, and death.[54] In general, serum or plasma valproic acid concentrations are in a range of 20–100 mg/l during controlled therapy, but may reach 150–1500 mg/l following acute poisoning. Monitoring of the serum level is often accomplished using commercial immunoassay techniques, although some laboratories employ gas or liquid chromatography.[55] In contrast to other antiepileptic drugs, at present there is little favorable evidence for salivary therapeutic drug monitoring. Salivary levels of valproic acid correlate poorly with serum levels, partly due to valproate's weak acid property (pKa of 4.9).[56]

In severe intoxication, hemoperfusion or hemofiltration can be an effective means of hastening elimination of the drug from the body.[57][58] Supportive therapy should be given to all patients experiencing an overdose and urine output should be monitored.[22] Supplemental L-carnitine is indicated in patients having an acute overdose[59][60] and also prophylactically[59] in high risk patients. Acetyl-L-carnitine lowers hyperammonemia less markedly[61] than L-carnitine.

## Interactions

Valproate inhibits CYP2C9, glucuronyl transferase, and epoxide hydrolase and is highly protein bound and hence may interact with drugs that are substrates for any of these enzymes or are highly protein bound themselves.[24] It may also potentiate the CNS depressant effects of alcohol.[24] It should not be given in conjunction with other antiepileptics due to the potential for reduced clearance of other antiepileptics (including carbamazepine, lamotrigine, phenytoin and phenobarbitone) and itself.[24] It may also interact with:[22][24][62]

* Aspirin: may increase valproate concentrations. May also interfere with valproate's metabolism.
* Benzodiazepines: may cause CNS depression and there are possible pharmacokinetic interactions.
* Carbapenem antibiotics: reduce valproate levels, potentially leading to seizures.
* Cimetidine: inhibits valproate's metabolism in the liver, leading to increased valproate concentrations.
* Erythromycin: inhibits valproate's metabolism in the liver, leading to increased valproate concentrations.
* Ethosuximide: valproate may increase ethosuximide concentrations and lead to toxicity.
* Felbamate: may increase plasma concentrations of valproate.
* Mefloquine: may increase valproate metabolism combined with the direct epileptogenic effects of mefloquine.
* Oral contraceptives: may reduce plasma concentrations of valproate.
* Primidone: may accelerate metabolism of valproate, leading to a decline of serum levels and potential breakthrough seizure.
* Rifampicin: increases the clearance of valproate, leading to decreased valproate concentrations
* Warfarin: valproate may increase free warfarin concentration and prolong bleeding time.
* Zidovudine: valproate may increase zidovudine serum concentration and lead to toxicity.

## Pharmacology

### Pharmacodynamics

Although the mechanism of action of valproate is not fully understood,[24] traditionally, its anticonvulsant effect has been attributed to the blockade of voltage-gated sodium channels and increased brain levels of gamma-aminobutyric acid (GABA).[24] The GABAergic effect is also believed to contribute towards the anti-manic properties of valproate.[24] In animals, sodium valproate raises cerebral and cerebellar levels of the inhibitory synaptic neurotransmitter, GABA, possibly by inhibiting GABA degradative enzymes, such as GABA transaminase, succinate-semialdehyde dehydrogenase and by inhibiting the re-uptake of GABA by neuronal cells.[24]

Prevention of neurotransmitter-induced hyperexcitability of nerve cells, via Kv7.2 channel and AKAP5, may also contribute to its mechanism.[63] Also, it has been shown to protect against a seizure-induced reduction in phosphatidylinositol (3,4,5)-trisphosphate (PIP3) as a potential therapeutic mechanism.[64]

It also has histone-deacetylase-inhibiting effects. The inhibition of histone deacetylase, by promoting more transcriptionally active chromatin structures, likely presents the epigenetic mechanism for regulation of many of the neuroprotective effects attributed to valproic acid. Intermediate molecules mediating these effects include VEGF, BDNF, and GDNF.[65][66]

#### Endocrine actions

Valproic acid has been found to be an antagonist of the androgen and progesterone receptors, and hence as a nonsteroidal antiandrogen and antiprogestogen, at concentrations much lower than therapeutic serum levels.[67] In addition, the drug has been identified as a potent aromatase inhibitor, and suppresses estrogen concentrations.[68] These actions are likely to be involved in the reproductive endocrine disturbances seen with valproic acid treatment.[67][68]

Valproic acid has been found to directly stimulate androgen biosynthesis in the gonads via inhibition of histone deacetylases and has been associated with hyperandrogenism in women and increased 4-androstenedione levels in men.[69][70] High rates of polycystic ovary syndrome and menstrual disorders have also been observed in women treated with valproic acid.[70]

### Pharmacokinetics

Some metabolites of valproic acid. Glucuronidation and β-oxidation are the main metabolic pathways; ω-oxidation metabolites are considered hepatotoxic.[71][72] Details see text.

Taken by mouth, valproate is rapidly and virtually completely absorbed from the gut.[71] When in the bloodstream, 80–90% of the substance are bound to plasma proteins, mainly albumin. Protein binding is saturable: it decreases with increasing valproate concentration, low albumin concentrations, the patient's age, additional use of other drugs such as aspirin, as well as liver and kidney impairment.[73][74] Concentrations in the cerebrospinal fluid and in breast milk are 1 to 10% of blood plasma concentrations.[71]

The vast majority of valproate metabolism occurs in the liver.[75] Valproate is known to be metabolized by the cytochrome P450 enzymes CYP2A6, CYP2B6, CYP2C9, and CYP3A5.[75] It is also known to be metabolized by the UDP-glucuronosyltransferase enzymes UGT1A3, UGT1A4, UGT1A6, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B15.[75] Some of the known metabolites of valproate by these enzymes and uncharacterized enzymes include (see image):[75]

* via glucuronidation (30–50%): valproic acid β-O-glucuronide
* via beta oxidation (>40%): 2E-ene-valproic acid, 2Z-ene-valproic acid, 3-hydroxyvalproic acid, 3-oxovalproic acid
* via omega oxidation: 5-hydroxyvalproic acid, 2-propyl-glutaric acid
* some others: 3E-ene-valproic acid, 3Z-ene-valproic acid, 4-ene-valproic acid, 4-hydroxyvalproic acid

All in all, over 20 metabolites are known.[71]

In adult patients taking valproate alone, 30–50% of an administered dose is excreted in urine as the glucuronide conjugate.[75] The other major pathway in the metabolism of valproate is mitochondrial beta oxidation, which typically accounts for over 40% of an administered dose.[75] Typically, less than 20% of an administered dose is eliminated by other oxidative mechanisms.[75] Less than 3% of an administered dose of valproate is excreted unchanged (i.e., as valproate) in urine.[75] Only a small amount is excreted via the faeces.[71] Elimination half-life is 16±3 hours and can decrease to 4–9 hours when combined with enzyme inducers.[71][74]

## Chemistry

Valproic acid is a branched short-chain fatty acid and the 2-n-propyl derivative of valeric acid.[5]

## History

Valproic acid was first synthesized in 1882 by Beverly S. Burton as an analogue of valeric acid, found naturally in valerian.[76] Valproic acid is a carboxylic acid, a clear liquid at room temperature. For many decades, its only use was in laboratories as a "metabolically inert" solvent for organic compounds. In 1962, the French researcher Pierre Eymard serendipitously discovered the anticonvulsant properties of valproic acid while using it as a vehicle for a number of other compounds that were being screened for antiseizure activity. He found it prevented pentylenetetrazol-induced convulsions in laboratory rats.[77] It was approved as an antiepileptic drug in 1967 in France and has become the most widely prescribed antiepileptic drug worldwide.[78] Valproic acid has also been used for migraine prophylaxis and bipolar disorder.[79]

## Society and culture

Valproate is available as a generic medication.[2]

### Approval status

Indications  |
FDA-labelled indication?[1] |
TGA-labelled indication?[12] |
MHRA-labelled indication?[80] | Literature support

|
|
|
|

Epilepsy | Yes | Yes | Yes | Limited (depends on the seizure type; it can help with certain kinds of seizures: drug-resistant epilepsy, partial and absence seizures, can be used against glioblastoma and other tumors both to improve survival and treat seizures, and against tonic–clonic seizures and status epilepticus).[81][82][83][84]
Bipolar mania | Yes | Yes | Yes | Limited.[85]
Bipolar depression | No | No | No | Moderate.[86]
Bipolar maintenance | No | No | No | Limited.[87]
Migraine prophylaxis | Yes | Yes (accepted) | No | Limited.
Acute migraine management | No | No | No | Only negative results.[88]
Schizophrenia | No | No | No | Weak evidence.[89]
Agitation in dementia | No | No | No | Weak evidence. Not recommended for agitation in people with dementia.[90] Increased rate of adverse effects, including a risk of serious adverse effects.[90]
Fragile X syndrome | Yes (orphan) | No | No | Limited.[66]
Familial adenomatous polyposis | Yes (orphan) | No | No | Limited.
Chronic pain & fibromyalgia | No | No | No | Limited.[91]
Alcohol hallucinosis | No | No | No | One randomised double-blind placebo-controlled trial.[92]
Intractable hiccups | No | No | No | Limited, five case reports support its efficacy, however.[93]
Non-epileptic myoclonus | No | No | No | Limited, three case reports support its efficacy, however.[94]
Cluster headaches | No | No | No | Limited, two case reports support its efficacy.[95]
West syndrome | No | No | No | A prospective clinical trial supported its efficacy in treating infantile spasms.[96]
HIV infection eradication | No | No | No | Double-blind placebo-controlled trials have been negative.[97][98][99]
Acute myeloid leukaemia | No | No | No | Two clinical trials have confirmed its efficacy in this indication as both a monotherapy and as an adjunct to tretinoin.[100][101][102]
Cervical cancer | No | No | No | One clinical trial supports its use here.[103]
Malignant melanoma | No | No | No | One phase II study has seemed to discount its efficacy.[104]
Breast cancer | No | No | No | A phase II study has supported its efficacy.[105]
Impulse control disorder | No | No | No | Limited.[106][107]

### Off-label uses

In 2012, pharmaceutical company Abbott paid $1.6 billion in fines to US federal and state governments for illegal promotion of off-label uses for Depakote, including the sedation of elderly nursing home residents.[108][109]

Some studies have suggested that valproate may reopen the critical period for learning absolute pitch and possibly other skills such as language.[110][111]

### Formulations

Sodium valproate

Clinical data
Other names| valproate sodium (USAN US)
License data|

* US DailyMed: Valproate_sodium

Identifiers

IUPAC name

* sodium 2-propylpentanoate

CAS Number|

* 1069-66-5 Y

PubChem CID|

* 16760703

DrugBank|

* DBSALT001257 Y

ChemSpider|

* 13428 Y

UNII|

* 5VOM6GYJ0D

KEGG|

* D00710 Y

ChEBI|

* CHEBI:9925 Y

ChEMBL|

* ChEMBL433 Y

Chemical and physical data
Formula| C8H15NaO2
Molar mass| 166.196 g·mol−1
3D model (JSmol)|

* Interactive image

SMILES

* CCCC(CCC)C(=O)[O-].[Na+]

InChI

* InChI=1S/C8H16O2.Na/c1-3-5-7(6-4-2)8(9)10;/h7H,3-6H2,1-2H3,(H,9,10);/q;+1/p-1 Y

* Key:AEQFSUDEHCCHBT-UHFFFAOYSA-M Y

(verify)
Valproate semisodiumClinical data

Trade names| Depakote, others
Other names| semisodium valproate, divalproex sodium (USAN US)
License data|

* US DailyMed: Divalproex_sodium

Identifiers

IUPAC name

* sodium;2-propylpentanoate;2-propylpentanoic acid

CAS Number|

* 76584-70-8 Y

PubChem CID|

* 23663956

DrugBank|

* DBSALT000185 Y

ChemSpider|

* 48337 Y

UNII|

* 644VL95AO6

KEGG|

* D00304 Y

ChEBI|

* CHEBI:4667 Y

ChEMBL|

* ChEMBL2105613 Y

Chemical and physical data
Formula| C16H31NaO4
Molar mass| 310.410 g·mol−1
3D model (JSmol)|

* Interactive image

SMILES

* CCCC(CCC)C(=O)O.CCCC(CCC)C(=O)[O-].[Na+]

InChI

* InChI=1S/2C8H16O2.Na/c2*1-3-5-7(6-4-2)8(9)10;/h2*7H,3-6H2,1-2H3,(H,9,10);/q;;+1/p-1 Y

* Key:MSRILKIQRXUYCT-UHFFFAOYSA-M Y

Valproate exists in two main molecular variants: sodium valproate and valproic acid without sodium (often implied by simply valproate). A mixture between these two is termed semisodium valproate. It is unclear whether there is any difference in efficacy between these variants, except from the fact that about 10% more mass of sodium valproate is needed than valproic acid without sodium to compensate for the sodium itself.[112]

#### Brand names of valproic acid

Branded products include:

* Absenor (Orion Corporation Finland)
* Convulex (G.L. Pharma GmbH Austria)
* Depakene (Abbott Laboratories in US and Canada)[113]
* Depakine (Sanofi Aventis France)
* Depakine (Sanofi Synthelabo Romania)
* Depalept (Sanofi Aventis Israel)
* Deprakine (Sanofi Aventis Finland)
* Encorate (Sun Pharmaceuticals India)
* Epival (Abbott Laboratories US and Canada)
* Epilim (Sanofi Synthelabo Australia and South Africa)
* Stavzor (Noven Pharmaceuticals Inc.)
* Valcote (Abbott Laboratories Argentina)
* Valpakine (Sanofi Aventis Brazil)
* Orfiril (Desitin Arzneimittel GmbH Norway)

#### Brand names of sodium valproate

##### Portugal

* Tablets - Diplexil-R by Bial.

##### United States

* Intravenous injection - Depacon by Abbott Laboratories.
* Syrup - Depakene by Abbott Laboratories. (Note Depakene capsules are valproic acid).
* Depakote tablets are a mixture of sodium valproate and valproic acid.
* Tablets - Eliaxim by Bial.

##### Australia

* Epilim Crushable Tablets Sanofi[114]
* Epilim Sugar Free Liquid Sanofi[114]
* Epilim Syrup Sanofi[114]
* Epilim Tablets Sanofi[114]
* Sodium Valproate Sandoz Tablets Sanofi
* Valpro Tablets Alphapharm
* Valproate Winthrop Tablets Sanofi
* Valprease tablets Sigma

##### New Zealand

* Epilim by Sanofi-Aventis

All the above formulations are Pharmac-subsidised.[115]

##### UK

* Depakote Tablets (as in USA)
* Tablets - Orlept by Wockhardt and Epilim by Sanofi
* Oral solution - Orlept Sugar Free by Wockhardt and Epilim by Sanofi
* Syrup - Epilim by Sanofi-Aventis
* Intravenous injection - Epilim Intravenous by Sanofi
* Extended release tablets - Epilim Chrono by Sanofi is a combination of sodium valproate and valproic acid in a 2.3:1 ratio.
* Enteric-coated tablets - Epilim EC200 by Sanofi is a 200-mg sodium valproate enteric-coated tablet.

###### UK only

* Capsules - Episenta prolonged release by Beacon
* Sachets - Episenta prolonged release by Beacon
* Intravenous solution for injection - Episenta solution for injection by Beacon

##### Germany, Switzerland, Norway, Finland, Sweden

* Tablets - Orfiril by Desitin Pharmaceuticals
* Intravenous injection - Orfiril IV by Desitin Pharmaceuticals

##### South Africa

* Syrup - Convulex by Byk Madaus[116]
* Tablets - Epilim by Sanofi-synthelabo

##### Malaysia

* Tablets - Epilim by Sanofi-Aventis

##### Romania

* Companies are SANOFI-AVENTIS FRANCE, GEROT PHARMAZEUTIKA GMBH and DESITIN ARZNEIMITTEL GMBH
* Types are Syrup, Extended release mini tablets, Gastric resistant coated tablets, Gastric resistant soft capsules, Extended release capsules, Extended release tablets and Extended release coated tablets

##### Canada

* Intravenous injection - Epival or Epiject by Abbott Laboratories.
* Syrup - Depakene by Abbott Laboratories its generic formulations include Apo-Valproic and ratio-Valproic.

##### Japan

* Tablets - Depakene by Kyowa Hakko Kirin
* Extended release tablets - Depakene-R by Kyowa Hakko Kogyo and Selenica-R by Kowa
* Syrup - Depakene by Kyowa Hakko Kogyo

##### Europe

In much of Europe, Dépakine and Depakine Chrono (tablets) are equivalent to Epilim and Epilim Chrono above.

##### Taiwan

* Tablets (white round tablet) – Depakine (Template:Zh-cp) by Sanofi Winthrop Industrie (France)

##### Iran

* Tablets – Epival 200 (enteric coated tablet) and Epival 500 (extended release tablet) by Iran Najo
* Slow release tablets – Depakine Chrono by Sanofi Winthrop Industrie (France)

##### Israel

Depalept and Depalept Chrono (extended release tablets) are equivalent to Epilim and Epilim Chrono above. Manufactured and distributed by Sanofi-Aventis.

##### India, Russia and CIS countries

* Valparin Chrono by Torrent Pharmaceuticals India
* Valprol CR by Intas Pharmaceutical (India)
* Encorate Chrono by Sun Pharmaceutical (India)
* Serven Chrono by Leeven APL Biotech (India)

#### Brand names of valproate semisodium

* Brazil - Depakote by Abbott Laboratories and Torval CR by Torrent do Brasil
* Canada - Epival by Abbott Laboratories
* Mexico - Epival and Epival ER (extended release) by Abbott Laboratories
* United Kingdom - Depakote (for psychiatric conditions) and Epilim (for epilepsy) by Sanofi-Aventis and generics
* United States - Depakote and Depakote ER (extended release) by Abbott Laboratories and generics[22]
* India - Valance and Valance OD by Abbott Healthcare Pvt Ltd, Divalid ER by Linux laboratories Pvt Ltd, Valex ER by Sigmund Promedica, Dicorate by Sun Pharma
* Germany - Ergenyl Chrono by Sanofi-Aventis and generics
* Chile - Valcote and Valcote ER by Abbott Laboratories
* France and other European countries -- Depakote
* Peru - Divalprax by AC Farma Laboratories
* China - Diprate OD

## References

1. ↑ 1.0 1.1 1.2 1.3 "Depakene, Stavzor (valproic acid) dosing, indications, interactions, adverse effects, and more". WebMD. http://reference.medscape.com/drug/depakene-stavzor-valproic-acid-343024#showall.
2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 "Valproic Acid". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/valproic-acid.html.
3. ↑ "Valproate banned without the pregnancy prevention programme". https://www.gov.uk/government/news/valproate-banned-without-the-pregnancy-prevention-programme.
4. ↑ "Pharmacology of valproate". Psychopharmacol Bull 37 Suppl 2: 17–24. 2003. PMID 14624230.
5. ↑ 5.0 5.1 5.2 "Valproic acid pathway: pharmacokinetics and pharmacodynamics". Pharmacogenet. Genomics 23 (4): 236–241. April 2013. doi:10.1097/FPC.0b013e32835ea0b2. PMID 23407051.
6. ↑ "Valproic acid". University of Alberta. 29 July 2017. https://www.drugbank.ca/drugs/DB00313.
7. ↑ Scott, D.F. (1993). The history of epileptic therapy : an account of how medication was developed (1. publ. ed.). Carnforth u.a.: Parthenon Publ. Group. p. 131. ISBN 9781850703914. https://books.google.com/books?id=8DlOOps7D4oC&pg=PA131.
8. ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
9. ↑ "The Top 300 of 2019". https://clincalc.com/DrugStats/Top300Drugs.aspx.
10. ↑ "Divalproex Sodium - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/DivalproexSodium.
11. ↑ Brayfield, Alison, ed. Martindale: The Complete Drug Reference. London: Pharmaceutical Press. https://www.medicinescomplete.com/mc/martindale/current/ms-10447-z.htm. Retrieved March 3, 2018.
12. ↑ 12.0 12.1 12.2 Rossi, S, ed (2013). Australian Medicines Handbook (2013 ed.). Adelaide: The Australian Medicines Handbook Unit Trust. ISBN 978-0-9805790-9-3.
13. ↑ "Basic pharmacology of valproate: a review after 35 years of clinical use for the treatment of epilepsy". CNS Drugs 16 (10): 669–694. 2002. doi:10.2165/00023210-200216100-00003. PMID 12269861.
14. ↑ "Valproate is an effective, well-tolerated drug for treatment of status epilepticus/serial attacks in adults". Acta Neurol. Scand. Suppl. 187: 51–4. 2007. doi:10.1111/j.1600-0404.2007.00847.x. PMID 17419829.
15. ↑ "The role of intravenous valproate in convulsive status epilepticus in the future". Acta Neurol Taiwan 19 (2): 78–81. 2010. PMID 20830628. http://www.ant.org.tw/Mag_Files/19-2/N201072314227_192edi.pdf.
16. ↑ "Valproate Information". Fda.gov. https://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm192645.htm.
17. ↑ Jochim, Janina; Rifkin-Zybutz, Raphael; Geddes, John; Cipriani, Andrea (7 October 2019). "Valproate for acute mania". Cochrane Database of Systematic Reviews 10: CD004052. doi:10.1002/14651858.CD004052.pub2. PMID 31621892.
18. ↑ 18.0 18.1 Wang, Y; Xia, J; Helfer, B (2016). "Valproate for schizophrenia". Cochrane Database of Systematic Reviews 11: CD004028.pub4. doi:10.1002/14651858.CD004028.pub4. PMID 27884042. PMC 6734130. http://www.cochrane.org/CD004028/SCHIZ_valproate-schizophrenia. Retrieved 2017-07-27.
19. ↑ "Gambling disorder during dopamine replacement treatment in Parkinson's disease: a comprehensive review". Biomed Res Int 2014: 1–9. 2014. doi:10.1155/2014/728038. PMID 25114917.
20. ↑ "Treatment of cognitive, psychiatric, and affective disorders associated with Parkinson's disease". Neurotherapeutics 11 (1): 78–91. 2014. doi:10.1007/s13311-013-0238-x. PMID 24288035.
21. ↑ "Impulsive and compulsive behaviors in Parkinson's disease". Annu Rev Clin Psychol 10: 553–80. 2014. doi:10.1146/annurev-clinpsy-032813-153705. PMID 24313567.
22. ↑ 22.0 22.1 22.2 22.3 22.4 22.5 22.6 22.7 22.8 "Depakote- divalproex sodium tablet, delayed release". http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=08a65cf4-7749-4ceb-6895-8f4805e2b01f.
23. ↑ "New perspectives of valproic acid in clinical practice". Expert Opin Investig Drugs 22 (12): 1535–1547. 2013. doi:10.1517/13543784.2013.853037. PMID 24160174.
24. ↑ 24.00 24.01 24.02 24.03 24.04 24.05 24.06 24.07 24.08 24.09 24.10 24.11 24.12 24.13 24.14 "Valpro sodium valproate" (PDF). Alphapharm Pty Limited. 16 December 2013. https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-04603-3.
25. ↑ "Depakote 250mg Tablets - Summary of Product Characteristics". Sanofi. 28 November 2013. http://www.medicines.org.uk/emc/medicine/25929/SPC/Depakote+250mg+Tablets/.
26. ↑ "Effects of valproic acid on longitudinal bone growth". J Child Neurol 19 (1): 26–30. 2004. doi:10.1177/088307380401900105011. PMID 15032379.
27. ↑ "Inhibition of cartilage growth by the anticonvulsant drugs diphenylhydantoin and sodium valproate". Br J Exp Pathol 69 (1): 17–22. 1988. PMID 3126792.
28. ↑ "Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy". Epilepsia 42 (9): 1141–7. 2002. doi:10.1046/j.1528-1157.2001.416800.x. PMID 11580761.
29. ↑ "Long-term valproate and lamotrigine treatment may be a marker for reduced growth and bone mass in children with epilepsy". Epilepsia 42 (9): 1141–7. 2002. doi:10.1046/j.1528-1157.2001.416800.x. PMID 11580761.
30. ↑ "Could Depakote cause Mydriasis". eHealthMe.com. 2014-11-18. http://www.ehealthme.com/ds/depakote/mydriasis.
31. ↑ Bilo, Leonilda; Meo, Roberta (October 2008). "Polycystic ovary syndrome in women using valproate: a review". Gynecological Endocrinology 24 (10): 562–70. doi:10.1080/09513590802288259. PMID 19012099.
32. ↑ Chukwu, J; Delanty, N; Webb, D; Cavalleri, GL (January 2014). "Weight change, genetics and antiepileptic drugs". Expert Review of Clinical Pharmacology 7 (1): 43–51. doi:10.1586/17512433.2014.857599. PMID 24308788.
33. ↑ New evidence in France of harm from epilepsy drug valproate BBC, 2017
34. ↑ "[Anti-epileptic agents during pregnancy. A prospective study on the course of pregnancy, malformations and child development]" (in de). Dtsch. Med. Wochenschr. 108 (7): 250–7. February 1983. doi:10.1055/s-2008-1069536. PMID 6402356.
35. ↑ "A clinical study of 57 children with fetal anticonvulsant syndromes". J. Med. Genet. 37 (7): 489–97. July 2000. doi:10.1136/jmg.37.7.489. PMID 10882750.
36. ↑ "Valproic acid in pregnancy: how much are we endangering the embryo and fetus?". Reprod. Toxicol. 28 (1): 1–10. 2009. doi:10.1016/j.reprotox.2009.02.014. PMID 19490988.
37. ↑ "Fetal valproate syndrome". Indian J Pediatr 73 (10): 937–939. 2006. doi:10.1007/bf02859291. PMID 17090909.
38. ↑ "The longer term outcome of children born to mothers with epilepsy". J. Neurol. Neurosurg. Psychiatry 75 (11): 1575–83. November 2004. doi:10.1136/jnnp.2003.029132. PMID 15491979. "This argues that the fetal valproate syndrome constitutes a real clinical entity that includes developmental delay and cognitive impairments, but that some children might exhibit some developmental delay without marked dysmorphism.".
39. ↑ "Simultaneous folate intake may prevent adverse effect of valproic acid on neurulating nervous system". Childs Nerv Syst 28 (5): 729–737. 2012. doi:10.1007/s00381-011-1673-9. PMID 22246336.
40. ↑ Cassels, Caroline (December 8, 2006). "NEAD: In Utero Exposure To Valproate Linked to Poor Cognitive Outcomes in Kids". Medscape. http://www.medscape.com/viewarticle/549073.
41. ↑ "In utero antiepileptic drug exposure: fetal death and malformations". Neurology 67 (3): 407–412. 2006. doi:10.1212/01.wnl.0000227919.81208.b2. PMID 16894099.
42. ↑ "Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism". JAMA 309 (16): 1696–1703. 2013. doi:10.1001/jama.2013.2270. PMID 23613074.
43. ↑ "Characteristics of fetal anticonvulsant syndrome associated autistic disorder". Dev Med Child Neurol 47 (8): 551–5. August 2005. doi:10.1017/S0012162205001076. PMID 16108456.
44. ↑ Autism Society of America: About Autism
45. ↑ I.Q. Harmed by Epilepsy Drug in Utero By RONI CARYN RABIN, New York Times, April 15, 2009
46. ↑ "Cognitive function at 3 years of age after fetal exposure to antiepileptic drugs". N. Engl. J. Med. 360 (16): 1597–1605. 2009. doi:10.1056/NEJMoa0803531. PMID 19369666.
47. ↑ Valproate Products: Drug Safety Communication - Risk of Impaired Cognitive Development in Children Exposed In Utero (During Pregnancy) . FDA. June 2011
48. ↑ Luat, AF (20 September 2007). "Paroxysmal tonic upgaze of childhood with co-existent absence epilepsy". Epileptic Disorders 9 (3): 332–6. doi:10.1684/epd.2007.0119. PMID 17884759.
49. ↑ Ouvrier, RA (July 1988). "Benign paroxysmal tonic upgaze of childhood". Journal of Child Neurology 3 (3): 177–80. doi:10.1177/088307388800300305. PMID 3209843.
50. ↑ Valproate Not To Be Used for Migraine During Pregnancy, FDA Warns
51. ↑ "New measures to avoid valproate exposure in pregnancy endorsed". 31 May 2018. https://www.ema.europa.eu/en/medicines/human/referrals/valproate-related-substances-0.
52. ↑ 52.0 52.1 52.2 52.3 Bentley, Suzanne (Dec 11, 2013). "Valproic Acid Level". Medscape. http://emedicine.medscape.com/article/2090462-overview.
53. ↑ 53.0 53.1 53.2 53.3 "Free Valproic Acid Assay (Reference – 2013.03.006) Notice of Assessment". Canadian Agency for Drugs and Technologies in Health (CADTH) with INESSS's permission. April 2014. https://www.cadth.ca/media/pdf/lab-tests/06_Free_Valproic_Acid_Assay_e.pdf.
54. ↑ Rissardo, Jamir Pitton; Caprara, Ana Letícia Fornari; Durante, Ícaro (2021). "Valproate-associated Movement Disorder: A Literature Review" (in en). Prague Medical Report 122 (3): 140–180. doi:10.14712/23362936.2021.14. ISSN 1214-6994. https://pmr.lf1.cuni.cz/122/3/0140/.
55. ↑ "Valproic acid toxicity: overview and management". J. Toxicol. Clin. Toxicol. 40 (6): 789–801. 2002. doi:10.1081/CLT-120014645. PMID 12475192.
56. ↑ "Therapeutic drug monitoring of antiepileptic drugs by use of saliva". Ther Drug Monit 35 (1): 4–29. 2013. doi:10.1097/FTD.0b013e31827c11e7. PMID 23288091.
57. ↑ "Extracorporeal elimination in acute valproic acid poisoning". Clin Toxicol 47 (7): 609–616. 2009. doi:10.1080/15563650903167772. PMID 19656009.
58. ↑ R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 8th edition, Biomedical Publications, Foster City, CA, 2008, pp. 1622–1626.
59. ↑ 59.0 59.1 "Science review: carnitine in the treatment of valproic acid-induced toxicity - what is the evidence?". Crit Care 9 (5): 431–440. 2005. doi:10.1186/cc3742. PMID 16277730.
60. ↑ "Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy". Am J Health Syst Pharm 69 (1): 35–39. 2012. doi:10.2146/ajhp110049. PMID 22180549.
61. ↑ "Comparison of the effects of L-carnitine, D-carnitine and acetyl-L-carnitine on the neurotoxicity of ammonia". Biochem. Pharmacol. 46 (1): 159–164. 1993. doi:10.1016/0006-2952(93)90360-9. PMID 8347126.
62. ↑ Herzog, Andrew; Farina, Erin (June 9, 2005). "Serum Valproate Levels with Oral Contraceptive Use". Epilepsia 46 (6): 970–971. doi:10.1111/j.1528-1167.2005.00605.x. PMID 15946343.
63. ↑ Kay, Hee Yeon; Greene, Derek L.; Kang, Seungwoo; Kosenko, Anastasia; Hoshi, Naoto (2015-10-01). "M-current preservation contributes to anticonvulsant effects of valproic acid". The Journal of Clinical Investigation 125 (10): 3904–3914. doi:10.1172/JCI79727. ISSN 0021-9738. PMID 26348896.
64. ↑ "Seizure-induced reduction in PIP3 levels contributes to seizure-activity and is rescued by valproic acid". Neurobiol. Dis. 62: 296–306. 2014. doi:10.1016/j.nbd.2013.10.017. PMID 24148856.
65. ↑ "Valproic acid, a molecular lead to multiple regulatory pathways". Folia Biol. (Praha) 53 (2): 37–49. 2007. PMID 17448293. http://fb.cuni.cz/Data/files/folia_biologica/volume_53_2007_2/FB2007A0007.pdf. Retrieved 2014-02-13.
66. ↑ 66.0 66.1 "Therapeutic potential of mood stabilizers lithium and valproic acid: beyond bipolar disorder". Pharmacol. Rev. 65 (1): 105–142. 2013. doi:10.1124/pr.111.005512. PMID 23300133.
67. ↑ 67.0 67.1 "Valproate is an anti-androgen and anti-progestin". Steroids 70 (14): 946–53. 2005. doi:10.1016/j.steroids.2005.07.003. PMID 16165177. https://opus.lib.uts.edu.au/bitstream/10453/16875/1/2010000997.pdf.
68. ↑ 68.0 68.1 Wyllie's Treatment of Epilepsy: Principles and Practice. Lippincott Williams & Wilkins. 17 February 2012. pp. 288–. ISBN 978-1-4511-5348-4. https://books.google.com/books?id=j9t6Qg0kkuUC&pg=PA288-IA37.
69. ↑ Uchida, Hiroshi; Maruyama, Tetsuo; Arase, Toru; Ono, Masanori; Nagashima, Takashi; Masuda, Hirotaka; Asada, Hironori; Yoshimura, Yasunori (2005). "Histone acetylation in reproductive organs: Significance of histone deacetylase inhibitors in gene transcription". Reproductive Medicine and Biology 4 (2): 115–122. doi:10.1111/j.1447-0578.2005.00101.x. ISSN 1445-5781. PMID 29662388.
70. ↑ 70.0 70.1 Isojärvi, Jouko I T; Taubøll, Erik; Herzog, Andrew G (2005). "Effect of Antiepileptic Drugs on Reproductive Endocrine Function in Individuals with Epilepsy". CNS Drugs 19 (3): 207–223. doi:10.2165/00023210-200519030-00003. ISSN 1172-7047. PMID 15740176.
71. ↑ 71.0 71.1 71.2 71.3 71.4 71.5 (in German) Austria-Codex. Vienna: Österreichischer Apothekerverlag. 2021. Depakine chrono retard 300 mg Filmtabletten.
72. ↑ Kumar, S.; Wong, H.; Yeung, S. A.; Riggs, K. W.; Abbott, F. S.; Rurak, D. W. (2000). "Disposition of valproic acid in maternal, fetal, and newborn sheep. II: Metabolism and renal elimination". Drug Metabolism and Disposition: The Biological Fate of Chemicals 28 (7): 857–864. PMID 10859160.
73. ↑ (in de) Angewandte Arzneimitteltherapie. Springer. 2001. pp. 28–29. ISBN 3540413561.
74. ↑ 74.0 74.1 Valproate FDA Professional Drug Information. Accessed 2021-08-06.
75. ↑ 75.0 75.1 75.2 75.3 75.4 75.5 75.6 75.7 "Valproic Acid". Valproic Acid. University of Alberta. 31 August 2017.
76. ↑ "On the propyl derivatives and decomposition products of ethylacetoacetate". Am. Chem. J. 3: 385–395. 1882.
77. ↑ "[Pharmacodynamic properties of N-dipropylacetic acid]" (in fr). Thérapie 18: 435–438. 1963. PMID 13935231.
78. ↑ "Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience". CNS Drugs 16 (10): 695–714. 2002. doi:10.2165/00023210-200216100-00004. PMID 12269862.
79. ↑ "The history of valproate in clinical neuroscience". Psychopharmacol Bull 37 Suppl 2: 5–16. 2003. PMID 14624229.
80. ↑ Joint Formulary Committee (2013). British National Formulary (BNF) (65 ed.). London, UK: Pharmaceutical Press. ISBN 978-0-85711-084-8. https://archive.org/details/bnf65britishnati0000unse.
81. ↑ "An update on sodium valproate". Pharmacotherapy 5 (3): 171–84. May–June 1985. doi:10.1002/j.1875-9114.1985.tb03413.x. PMID 3927267.
82. ↑ Glauser, Tracy A; Cnaan, Avital; Shinnar, Shlomo; Hirtz, Deborah G; Dlugos, Dennis; Masur, David; Clark, Peggy O; Capparelli, Edmund V et al. (2010). "Ethosuximide, valproic acid, and lamotrigine in childhood absence epilepsy". New England Journal of Medicine 362 (9): 790–9. doi:10.1056/NEJMoa0902014. PMID 20200383.
83. ↑ Jiang, Mei (6 April 2015). "Co-Administration of Valproic Acid and Lamotrigine in the Treatment of Refractory Epilepsy (P1.238)". Neurology 84 (14 Supplement): P1.238. http://www.neurology.org/content/84/14_Supplement/P1.238.
84. ↑ Berendsen, S.; Kroonen, J.; Seute, T.; Snijders, T.; Broekman, M. L. D.; Spliet, W. G. M.; Willems, M.; Artesi, M. et al. (1 September 2014). "O9.06 * Prognostic Relevance and Oncogenic Correlates of Epilepsy in Glioblastoma Patients". Neuro-Oncology 16 (suppl_2): ii21. doi:10.1093/neuonc/nou174.77.
85. ↑ "Valproate in acute mania: is our practice evidence based?". International Journal of Health Care Quality Assurance 25 (1): 41–52. 2012. doi:10.1108/09526861211192395. PMID 22455007.
86. ↑ "Divalproex sodium versus placebo in the treatment of acute bipolar depression: a systematic review and meta-analysis". J Affect Disord 124 (3): 228–334. 2010. doi:10.1016/j.jad.2009.11.008. PMID 20044142.
87. ↑ "A review of valproate in psychiatric practice". Expert Opin Drug Metab Toxicol 5 (5): 539–51. 2009. doi:10.1517/17425250902911455. PMID 19409030.
88. ↑ "Use of intravenous valproic acid for acute migraine". Ann Pharmacother 42 (3): 403–7. 2008. doi:10.1345/aph.1K531. PMID 18303140.
89. ↑ Wang, Yijun; Xia, Jun; Helfer, Bartosz; Li, Chunbo; Leucht, Stefan (2016). "Valproate for schizophrenia". The Cochrane Database of Systematic Reviews 11: CD004028. doi:10.1002/14651858.CD004028.pub4. ISSN 1469-493X. PMID 27884042.
90. ↑ 90.0 90.1 Baillon, Sarah F.; Narayana, Usha; Luxenberg, Jay S.; Clifton, Andrew V. (2018-10-05). "Valproate preparations for agitation in dementia". The Cochrane Database of Systematic Reviews 2018 (10): CD003945. doi:10.1002/14651858.CD003945.pub4. ISSN 1469-493X. PMID 30293233.
91. ↑ "Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults". Cochrane Database Syst Rev (10): CD009183. 2011. doi:10.1002/14651858.CD009183.pub2. PMID 21975791.
92. ↑ "Valproate treatment of acute alcohol hallucinosis: a double-blind, placebo-controlled study". Alcohol Alcohol. 43 (4): 456–459. July–August 2008. doi:10.1093/alcalc/agn043. PMID 18495806.
93. ↑ "Treatment of intractable hiccups with valproic acid". Neurology 31 (11): 1458–60. 1981. doi:10.1212/WNL.31.11.1458. PMID 6796902.
94. ↑ "Valproic acid in the treatment of nonepileptic myoclonus". Arch. Neurol. 39 (7): 448–9. 1982. doi:10.1001/archneur.1982.00510190066025. PMID 6808975.
95. ↑ "Significance of migrainous features in cluster headache: divalproex responsiveness". Headache 38 (7): 547–51. July–August 1998. doi:10.1046/j.1526-4610.1998.3807547.x. PMID 15613172.
96. ↑ "Therapy of infantile spasms with valproate: results of a prospective study". Epilepsia 29 (5): 553–60. September–October 1988. doi:10.1111/j.1528-1157.1988.tb03760.x. PMID 2842127.
97. ↑ "Valproic acid and HIV-1 latency: beyond the sound bite". Retrovirology 2 (1): 56. 2005. doi:10.1186/1742-4690-2-56. PMID 16168066. PMC 1242254. http://www.retrovirology.com/content/pdf/1742-4690-2-56.pdf. Retrieved 2014-02-13.
98. ↑ "Valproic acid in association with highly active antiretroviral therapy for reducing systemic HIV-1 reservoirs: results from a multicentre randomized clinical study". HIV Med. 13 (5): 291–6. 2012. doi:10.1111/j.1468-1293.2011.00975.x. PMID 22276680.
99. ↑ "Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection". PLOS ONE 5 (2): e9390. 2010. doi:10.1371/journal.pone.0009390. PMID 20186346. Bibcode: 2010PLoSO...5.9390A.
100. ↑ "Clinical trial of valproic acid and all-trans retinoic acid in patients with poor-risk acute myeloid leukemia". Cancer 104 (12): 2717–2725. 2005. doi:10.1002/cncr.21589. PMID 16294345.
101. ↑ "The histone deacetylase (HDAC) inhibitor valproic acid as monotherapy or in combination with all-trans retinoic acid in patients with acute myeloid leukemia". Cancer 106 (1): 112–119. 2006. doi:10.1002/cncr.21552. PMID 16323176.
102. ↑ "Histone deacetylase inhibition in the treatment of acute myeloid leukemia: the effects of valproic acid on leukemic cells, and the clinical and experimental evidence for combining valproic acid with other antileukemic agents". Clin Epigenetics 5 (1): 12. 2013. doi:10.1186/1868-7083-5-12. PMID 23898968. PMC 3733883. http://www.clinicalepigeneticsjournal.com/content/pdf/1868-7083-5-12.pdf. Retrieved 2014-02-13.
103. ↑ "A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results". Med. Oncol. 28 Suppl 1: S540–6. 2011. doi:10.1007/s12032-010-9700-3. PMID 20931299.
104. ↑ "A phase I-II study of the histone deacetylase inhibitor valproic acid plus chemoimmunotherapy in patients with advanced melanoma". Br. J. Cancer 100 (1): 28–36. 2009. doi:10.1038/sj.bjc.6604817. PMID 19127265.
105. ↑ "Clinical and biological effects of valproic acid as a histone deacetylase inhibitor on tumor and surrogate tissues: phase I/II trial of valproic acid and epirubicin/FEC". Clin. Cancer Res. 15 (7): 2488–96. 2009. doi:10.1158/1078-0432.CCR-08-1930. PMID 19318486. http://clincancerres.aacrjournals.org/content/15/7/2488.full.pdf.
106. ↑ "Valproate for the treatment of medication-induced impulse-control disorders in three patients with Parkinson's disease". Parkinsonism Relat. Disord. 17 (5): 379–81. 2011. doi:10.1016/j.parkreldis.2011.03.003. PMID 21459656.
107. ↑ "Valproate as a treatment for dopamine dysregulation syndrome (DDS) in Parkinson's disease". J. Neurol. 260 (2): 521–7. 2013. doi:10.1007/s00415-012-6669-1. PMID 23007193.
108. ↑ Aizenman, N. C. (7 May 2012). "Abbott Laboratories to pay $1.6 billion over illegal marketing of Depakote". Washington Post. https://www.washingtonpost.com/national/health-science/abbott-laboratories-agrees-to-16-billion-settlement-over-marketing-of-depakote/2012/05/07/gIQAh5098T_story.html.
109. ↑ Schmidt, Michael; Thomas, Katie (8 May 2012). "Abbott settles marketing lawsuit". https://www.nytimes.com/2012/05/08/business/abbott-to-pay-1-6-billion-over-illegal-marketing.html.
110. ↑ "Valproate reopens critical-period learning of absolute pitch". Frontiers in Systems Neuroscience 7: 102. 2013. doi:10.3389/fnsys.2013.00102. PMID 24348349.
111. ↑ Thomson, Helen. "Learning drugs reawaken grown-up brain's inner child". New Scientist Ltd.. https://www.newscientist.com/article/dn24831-learning-drugs-reawaken-grown-up-brains-inner-child/.
112. ↑ David Taylor; Carol Paton; Shitij Kapur (2009). The Maudsley Prescribing Guidelines, Tenth Edition (10, revised ed.). CRC Press. p. 124. ISBN 9780203092835. https://books.google.com/books?id=pbvLBQAAQBAJ&pg=PA124.
113. ↑ "Depakene- valproic acid capsule, liquid filled". 19 September 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a0288919-75bf-4752-975f-40579572c0f7.
114. ↑ 114.0 114.1 114.2 114.3 "Australian product information epilim (sodium valproate) crushable tablets, enteric-coated tablets, syrup, liquid" (PDF). 15 April 2020. http://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-05620-3.
115. ↑ "Sodium valproate -- Pharmaceutical Schedule". Pharmaceutical Management Agency. http://www.pharmac.govt.nz/Schedule?osq=Sodium valproate.
116. ↑ South African Electronic Package Inserts: Convulex

## External links

* "Valproic acid". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/valproic acid.
* "Valproate sodium". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/sodium valproate.
* "Divalproex sodium". Drug Information Portal. U.S. National Library of Medicine. https://druginfo.nlm.nih.gov/drugportal/name/divalproex sodium.

* v
* t
* e

Anticonvulsants (N03)

GABAergics|

| GABAAR PAMs|

* Barbiturates: Barbexaclone
* Metharbital
* Methylphenobarbital
* Pentobarbital
* Phenobarbital#
* Primidone; Carbamates: Felbamate; Benzodiazepines: Clobazam
* Clonazepam
* Clorazepate
* Diazepam#
* Lorazepam#
* Midazolam
* Nimetazepam
* Nitrazepam
* Temazepam; Others: Bromide (potassium bromide, sodium bromide)
* Imepitoin
* Paraldehyde
* Stiripentol

|

GABA-T inhibitors|

* Fatty acids (and related): Valproate
* Valpromide
* Valproate pivoxil
* Vigabatrin

Others|

* GABAR agonists: Progabide; GAT-1 inhibitors: Tiagabine

Channel
modulators|

| Sodium blockers|

* Hydantoins: Ethotoin
* Fosphenytoin
* Mephenytoin
* Phenytoin#; Ureides: Acetylpheneturide
* Chlorphenacemide
* Phenacemide‡
* Pheneturide; Fatty acids: Valproate
* Valpromide
* Valproate pivoxil; Carboxamides: Carbamazepine#
* Eslicarbazepine acetate
* Oxcarbazepine; Others: Lacosamide
* Lamotrigine#
* Rufinamide
* Topiramate
* Zonisamide

|

Calcium blockers|

* Oxazolidinediones: Ethadione
* Paramethadione
* Trimethadione; Succinimides: Ethosuximide#
* Mesuximide
* Phensuximide; Gabapentinoids: Gabapentin
* Pregabalin; Others: Imepitoin
* Lamotrigine#
* Topiramate
* Zonisamide

Potassium openers|

* Retigabine

Others|

| CA inhibitors|

* Sulfonamides: Acetazolamide
* Ethoxzolamide
* Sultiame
* Topiramate
* Zonisamide

|

Others|

* Albutoin
* Beclamide
* Brivaracetam
* Cannabidiol
* Etiracetam
* Levetiracetam
* Perampanel

* #WHO-EM
* ‡Withdrawn from market
* Clinical trials:
* †Phase III
* §Never to phase III

* v
* t
* e

Mood stabilizers

Anticonvulsants|

* Carbamazepine
* Lamotrigine
* Oxcarbazepine
* Valproate
* Valnoctamide
* Valproate pivoxil
* Valpromide

Atypical antipsychotics|

* Aripiprazole
* Cariprazine
* Clozapine
* Lurasidone
* Olanzapine (+fluoxetine)
* Paliperidone
* Quetiapine
* Risperidone
* Ziprasidone

Others|

* Ketamine
* Lithium (lithium acetate, lithium carbonate, lithium chloride, lithium citrate, lithium hydroxide, lithium orotate)
* Omega-3 fatty acids (docosahexaenoic acid, eicosapentaenoic acid)

Pharmacodynamics

* v
* t
* e

Androgen receptor modulators

AR|

| Agonists|

* Testosterone derivatives: 4-Androstenediol
* 4-Dehydroepiandrosterone (4-DHEA)
* 4-Hydroxytestosterone
* 4,17α-Dimethyltestosterone
* 5-Androstenedione
* 11-Ketotestosterone
* 11β-Hydroxyandrostenedione
* Adrenosterone (11-ketoandrostenedione, 11-oxoandrostenedione)
* Androstenediol (5-androstenediol)
* Androstenediol 3β-acetate
* Androstenediol 17β-acetate
* Androstenediol diacetate
* Androstenediol dipropionate
* Androstenedione (4-androstenedione)
* Atamestane
* Boldenone
* Boldenone undecylenate
* Boldione (1,4-androstadienedione)
* Clostebol
* Clostebol acetate
* Clostebol caproate
* Clostebol propionate
* Cloxotestosterone
* Cloxotestosterone acetate
* Dehydroandrosterone
* DHEA (androstenolone, prasterone; 5-DHEA)
* DHEA enanthate (prasterone enanthate)
* DHEA sulfate
* Exemestane
* Formestane
* Plomestane
* Quinbolone
* Silandrone
* Testosterone# (+dutasteride)
* Testosterone esters
* Polytestosterone phloretin phosphate

* Dihydrotestosterone derivatives: 1-Androstenediol
* 1-Androstenedione
* 1-Androsterone (1-andro, 1-DHEA)
* 1-Testosterone
* 3α-Androstanediol
* 5α-Androst-2-en-17-one
* 7β-Hydroxyepiandrosterone
* 11-Ketodihydrotestosterone
* Androsterone
* Bolazine
* Bolazine capronate
* Dihydroethisterone
* Dihydroethyltestosterone
* Dihydrofluoxymesterone
* Dihydromethylandrostenediol
* Dihydrotestosterone (DHT) (androstanolone, stanolone)
* Dihydrotestosterone esters
* Drostanolone
* Drostanolone propionate
* Epiandrosterone
* Epitiostanol
* Mepitiostane
* Mesabolone
* Mesterolone
* Mesterolone cipionate
* Methyldiazinol
* Nisterime
* Nisterime acetate
* Prostanozol
* Stenbolone
* Stenbolone acetate
* Testifenon (testiphenon, testiphenone)

* 19-Nortestosterone derivatives: 7α-Methyl-19-norandrostenedione (MENT dione, trestione)
* 11β-Methyl-19-nortestosterone
* 11β-Methyl-19-nortestosterone dodecylcarbonate
* 19-Nor-5-androstenediol
* 19-Nor-5-androstenedione
* 19-Nordehydroepiandrosterone
* Bolandiol
* Bolandiol dipropionate
* Bolandione (19-nor-4-androstenedione)
* Bolmantalate (nandrolone adamantoate)
* Dienedione
* Dienolone
* Dimethandrolone
* Dimethandrolone buciclate
* Dimethandrolone dodecylcarbonate
* Dimethandrolone undecanoate
* LS-1727 (nandrolone 17β-N-(2-chloroethyl)-N-nitrosocarbamate)
* Methoxydienone (methoxygonadiene)
* Nandrolone
* Nandrolone esters
* Norclostebol
* Norclostebol acetate
* Normethandrone (methylestrenolone, normethisterone)
* Oxabolone
* Oxabolone cipionate (oxabolone cypionate)
* Trenbolone
* Trenbolone acetate
* Trenbolone enanthate
* Trenbolone hexahydrobenzylcarbonate
* Trenbolone undecanoate
* Trendione
* Trestolone (MENT)
* Trestolone acetate
* Trestolone enanthate

* Dihydrotestosterone and 19-nortestosterone derivatives: 5α-Dihydrolevonorgestrel
* 5α-Dihydronandrolone
* 5α-Dihydronorethandrolone
* 5α-Dihydronorethisterone
* 5α-Dihydronormethandrone
* 5α-Dihydrotrestolone
* 19-Norandrosterone

* 17α-Alkylated testosterone derivatives: Bolasterone
* Calusterone
* Chlorodehydromethylandrostenediol (CDMA)
* Chlorodehydromethyltestosterone (CDMT)
* Chloromethylandrostenediol (CMA)
* Enestebol
* Ethyltestosterone
* Fluoxymesterone
* Formebolone
* Hydroxystenozole
* Metandienone (methandrostenolone)
* Methandriol (methylandrostenediol)
* Methandriol bisenanthoyl acetate
* Methandriol diacetate
* Methandriol dipropionate
* Methandriol propionate
* Methylclostebol (chloromethyltestosterone)
* Methyltestosterone (+esterified estrogens)
* Methyltestosterone 3-hexyl ether
* Oxymesterone
* Penmesterol
* Tiomesterone

* 17α-Alkylated dihydrotestosterone derivatives: Androisoxazole
* Desoxymethyltestosterone
* Furazabol
* Mebolazine (dimethazine)
* Mestanolone
* Metenolone
* Metenolone acetate
* Metenolone enanthate
* Methasterone
* Methyl-1-testosterone
* Methylepitiostanol
* Methylstenbolone
* Oxandrolone
* Oxymetholone
* Stanozolol

* 17α-Alkylated 19-nortestosterone derivatives: Bolenol
* Dimethyldienolone
* Dimethyltrienolone
* Ethyldienolone
* Ethylestrenol
* Methyldienolone
* Methylhydroxynandrolone (MOHN, MHN)
* Metribolone
* Mibolerone
* Norboletone
* Norethandrolone
* Propetandrol
* RU-2309
* Tetrahydrogestrinone

* 17α-Vinyltestosterone derivatives: Norvinisterone (vinylnortestosterone)
* Vinyltestosterone

* 17α-Ethynyltestosterone derivatives: Δ4-Tibolone
* Danazol
* Desogestrel
* Ethisterone (ethynyltestosterone)
* Etonogestrel
* Etynodiol
* Etynodiol diacetate
* Gestodene
* Gestrinone
* Levonorgestrel
* Levonorgestrel esters (e.g., levonorgestrel butanoate)
* Lynestrenol
* Lynestrenol phenylpropionate
* Norethisterone
* Norethisterone esters (e.g., norethisterone acetate, norethisterone enanthate)
* Norgestrel
* Norgestrienone
* Quingestanol
* Quingestanol acetate
* Tibolone

* Progesterone derivatives: Medroxyprogesterone acetate
* Megestrol acetate

* Others/unsorted: 3-Keto-5α-abiraterone
* 5α-Androstane
* Alternariol
* Cl-4AS-1
* Drupanol
* ZM-182345

|

Mixed
(SARMs)|

* Nonsteroidal: 198RL26
* ACP-105
* AC-262536
* Acetothiolutamide
* Andarine (acetamidoxolutamide, androxolutamide, GTx-007, S-4)
* BMS-564929
* DTIB
* Enobosarm (ostarine, MK-2866, GTx-024, S-22)
* FTBU-1
* GSK-4336A
* GSK-8698
* LG-121071 (LGD-121071)
* LGD-2226
* LGD-2941 (LGD-122941)
* LGD-3303
* LGD-4033
* JNJ-26146900
* JNJ-28330835
* JNJ-37654032
* ORM-11984
* R-1
* RAD140
* RU-59063
* S-1
* S-23
* S-40503
* S-101479
* Triclosan

* Steroidal: EM-9017
* MK-0773
* TFM-4AS-1
* YK-11

Antagonists|

* Steroidal: 7α-Thioprogesterone
* 7α-Thiospironolactone
* 7α-Thiomethylspironolactone
* 11α-Hydroxyprogesterone
* 15β-Hydroxycyproterone acetate
* Abiraterone
* Abiraterone acetate
* Allyltestosterone
* Benorterone
* BOMT
* Canrenoic acid
* Canrenone
* Chlormadinone acetate
* Clascoterone
* Clometerone
* Cyproheptadine
* Cyproterone
* Cyproterone acetate
* Delanterone
* Delmadinone acetate
* Dicirenone
* Dienogest
* Drospirenone
* DU-41165
* Edogestrone
* EM-4350
* EM-5854
* EM-5855
* EM-6537
* Epitestosterone
* Galeterone
* Guggulsterone
* Medrogestone
* Megestrol acetate
* Mespirenone
* Metogest
* Mexrenone
* Mifepristone
* Nomegestrol acetate
* Nordinone
* Osaterone
* Osaterone acetate
* Oxendolone
* Potassium canrenoate
* Promegestone
* Prorenone
* Rosterolone
* RU-15328
* SC-5233 (spirolactone)
* Spironolactone
* Spirorenone
* Spiroxasone
* Topterone
* Trimegestone
* Trimethyltrienolone (R-2956)
* Zanoterone

* Nonsteroidal: 5N-Bicalutamide
* AA560
* Antarlides
* Arabilin
* Apalutamide
* Atraric acid
* AZD-3514
* Bakuchiol
* BAY-1024767
* Bicalutamide
* Bisphenols (e.g., BADGE, BFDGE, bisphenol A, bisphenol F, bisphenol S)
* BMS-501949
* BMS-570511
* BMS-641988
* CH5137291
* Cimetidine
* Cioteronel
* Cyanonilutamide
* Darolutamide
* DDT (via metabolite p,p’-DDE)
* Dieldrin
* DIMP
* Endosulfan
* Enzalutamide
* EPI-001
* Fenarimol
* Flutamide
* Hydroxyflutamide
* Inocoterone
* Inocoterone acetate
* Ketoconazole
* Ketodarolutamide
* Lavender oil
* LG-105
* LG-120907
* LGD-1331
* Linuron
* Methiocarb
* N-Butylbenzenesulfonamide
* N-Desmethylapalutamide
* N-Desmethylenzalutamide
* Nilutamide
* ONC1-13B
* Pentomone
* PF-998425
* Phenothrin
* Prochloraz
* Procymidone
* Proxalutamide
* Ralaniten (EPI-002)
* Ralaniten acetate (EPI-506)
* RD-162
* Ro 2-7239
* Ro 5-2537
* RU-22930
* RU-56187
* RU-57073
* RU-58642
* RU-58841
* Seviteronel
* Thalidomide
* Topilutamide (fluridil)
* Valproic acid
* Vinclozolin
* YM-580
* YM-92088
* YM-175735

GPRC6A|

| Agonists|

* Cations (incl. aluminum, calcium, Gadolinium

|

See also
Receptor/signaling modulators
Androgens and antiandrogens
Estrogen receptor modulators
Progesterone receptor modulators
List of androgens/anabolic steroids

* v
* t
* e

Histone deacetylase inhibitors

* 3,3'-Diindolylmethane
* β-Hydroxybutyric acid (β-hydroxybutyrate)
* Abexinostat
* Acetoacetic acid (acetoacetate)
* Allyl mercaptan
* Apicidin
* Belinostat
* Butyric acid (butyrate)
* Capsaicin
* Chidamide
* Citarinostat
* Curcumin
* Diallyl disulfide
* Entinostat
* Fimepinostat
* Givinostat
* Indole-3-carbinol
* Kevetrin
* Martinostat
* Mocetinostat
* Nicotinamide
* Panobinostat
* Parthenolide
* Phenylbutyrate
* Pracinostat
* Quisinostat
* Resminostat
* Romidepsin
* Scriptaid
* Sodium butyrate
* Sodium oxybate (GHB sodium)
* Sodium phenylbutyrate
* Sodium valproate
* Sulforaphane
* Trapoxin B
* Trichostatin A
* Valnoctamide
* Valproic acid (valproate)
* Valproate pivoxil
* Valproate semisodium
* Valpromide
* Vorinostat (SAHA)

See also: Receptor/signaling modulators

* v
* t
* e

Ion channel modulators

Calcium|

| VDCCs|

| Blockers|

* L-type-selective: Dihydropyridines: Amlodipine
* Aranidipine
* Azelnidipine
* Barnidipine
* Clevidipine
* Cronidipine
* Darodipine
* Dexniguldipine
* Elgodipine
* Elnadipine
* Felodipine
* Flordipine
* Furnidipine
* Iganidipine
* Isradipine
* Lacidipine
* Lemildipine
* Lercanidipine
* Levamlodipine
* Levniguldipine
* Manidipine
* Mepirodipine
* Mesudipine
* Nicardipine
* Nifedipine
* Niguldipine
* Niludipine
* Nilvadipine
* Nimodipine
* Nisoldipine
* Nitrendipine
* Olradipine
* Oxodipine
* Palonidipine
* Pranidipine
* Ryodipine (riodipine)
* Sagandipine
* Sornidipine
* Teludipine
* Tiamdipine
* Trombodipine
* Vatanidipine; Diltiazem derivatives: Clentiazem
* Diltiazem
* Iprotiazem
* Nictiazem
* Siratiazem; Phenylalkylamines: Anipamil
* Dagapamil
* Devapamil
* Dexverapamil
* Emopamil
* Etripamil
* Falipamil
* Gallopamil
* Levemopamil
* Nexopamil
* Norverapamil
* Ronipamil
* Tiapamil
* Verapamil; Others: AH-1058
* Brinazarone
* Budiodarone
* Celivarone
* Cyproheptadine
* Dronedarone
* Fantofarone
* SR-33805
* Tetrahydropalmatine

* N-type-selective: ω-Conotoxins
* ω-Conotoxin GVIA
* Caroverine
* Huwentoxin XVI
* Leconotide (ω-conotoxin CVID)
* PD-173212
* Ralfinamide
* Safinamide
* Z160
* Ziconotide (ω-conotoxin MVIIA)

* P-type-selective: ω-Agatoxin IVA
* ω-Agatoxin IVB

* R-type-selective: SNX-482

* T-type-selective: ABT-639
* ML-218
* Niflumic acid
* NNC 55-0396
* ProTx I
* Z944
* Zonisamide

* Non-selective: ω-Agatoxin TK
* ω-Conotoxin MVIIC
* Benidipine
* Bepridil
* Cilnidipine
* Cinnarizine
* Dotarizine
* Efonidipine
* Flunarizine
* Lamotrigine
* Levetiracetam
* Lomerizine
* Loperamide
* Mibefradil
* NP078585
* Ruthenium red
* TROX-1

* α2δ subunit-selective (gabapentinoids): 4-Methylpregabalin
* Arbaclofen
* Arbaclofen placarbil
* Atagabalin
* Baclofen
* Gabapentin
* Gabapentin enacarbil
* Imagabalin
* Mirogabalin
* PD-200,347
* PD-217,014
* PD-299,685
* Phenibut
* Pregabalin

* Others/unsorted: Bencyclane
* Berbamine
* Bevantolol
* Canadine
* Carboxyamidotriazole
* Cycleanine
* Dauricine
* Dimeditiapramine
* Diproteverine
* Enpiperate
* Eperisone
* Elpetrigine
* Ethadione
* Ethanol (alcohol)
* Ethosuximide
* Fasudil
* Fendiline
* Fostedil
* Imepitoin
* JTV-519
* Lidoflazine
* Magnesium
* Manoalide
* Mesuximide
* Monatepil
* Naftopidil
* Ochratoxin A
* Osthol
* Otilonium bromide
* Paramethadione
* Phensuximide
* Pinaverium bromide
* Prenylamine
* Rhynchophylline
* Sesamodil
* Silperisone
* Sipatrigine
* Terodiline
* Tetrandrine
* Tolperisone
* Trimethadione
* Valperinol

|

Activators|

* L-type-selective: Bay K8644

Potassium|

| VGKCs|

| Blockers|

* 3,4-Diaminopyridine (amifampridine)
* 4-Aminopyridine (fampridine/dalfampridine)
* Adekalant
* Almokalant
* Amiodarone
* Azimilide
* Bretylium
* Bunaftine
* Charybdotoxin
* Clamikalant
* Conotoxins
* Dalazatide
* Dendrotoxin
* Dofetilide
* Dronedarone
* E-4031
* Hanatoxin
* HgeTx1
* HsTx1
* Ibutilide
* Inakalant
* Kaliotoxin
* Linopirdine
* Lolitrem B
* Maurotoxin
* Nifekalant
* Notoxin
* Paxilline
* Pinokalant
* Quinidine
* ShK-186
* Sotalol
* Tedisamil
* Terikalant
* Tetraethylammonium
* Vernakalant

* hERG (KCNH2, Kv11.1)-specific: Ajmaline
* Amiodarone
* AmmTX3
* Astemizole
* Azaspiracid
* AZD1305
* Azimilide
* Bedaquiline
* BeKm-1
* BmTx3
* BRL-32872
* Chlorpromazine
* Cisapride
* Clarithromycin
* Darifenacin
* Dextropropoxyphene
* Diallyl trisulfide
* Domperidone
* E-4031
* Ergtoxins
* Erythromycin
* Gigactonine
* Haloperidol
* Ketoconazole
* Norpropoxyphene
* Orphenadrine
* Pimozide
* PNU-282,987
* Promethazine
* Quinidine
* Ranolazine
* Roxithromycin
* Sertindole
* Solifenacin
* Tamulotoxin
* Terodiline
* Terfenadine
* Thioridazine
* Tolterodine
* Vanoxerine
* Vernakalant

* KCNQ (Kv7)-specific: Linopirdine
* XE-991
* Spooky toxin (SsTx)

|

Activators|

* KCNQ (Kv7)-specific: Flupirtine
* Retigabine

IRKs|

| Blockers|

* KATP-specific: Acetohexamide
* Carbutamide
* Chlorpropamide
* Glibenclamide (glyburide)
* Glibornuride
* Glicaramide
* Gliclazide
* Glimepiride
* Glipizide
* Gliquidone
* Glisoxepide
* Glyclopyramide
* Glycyclamide
* Metahexamide
* Mitiglinide
* Nateglinide
* Repaglinide
* Tolazamide
* Tolbutamide

* GIRK-specific: Barium
* Caramiphen
* Cloperastine
* Clozapine
* Dextromethorphan
* Ethosuximide
* Ifenprodil
* Tertiapin
* Tipepidine

|

Activators|

* KATP-specific: Aprikalim
* Bimakalim
* Cromakalim
* Diazoxide
* Emakalim
* Levcromakalim
* Mazokalim
* Minoxidil
* Naminidil
* Nicorandil
* Pinacidil
* Rilmakalim
* Sarakalim

* GIRK-specific: ML-297 (VU0456810)

KCa|

| Blockers|

* BKCa-specific: Ethanol (alcohol)
* GAL-021

|

Activators|

* BKCa-specific: Flufenamic acid
* Meclofenamic acid
* Niflumic acid
* Nimesulide
* Rottlerin (mallotoxin)
* Tolfenamic acid

K2Ps|

| Blockers|

* 12-O-Tetradecanoylphorbol-13-acetate
* Arachidonic acid
* Fluoxetine
* Norfluoxetine

|

Activators|

* Riluzole

Sodium|

| VGSCs|

| Blockers|

* Antianginals: Ranolazine

* Antiarrhythmics (class I): Ajmaline
* Aprindine
* Disopyramide
* Dronedarone
* Encainide
* Flecainide
* Lidocaine
* Lorajmine
* Lorcainide
* Mexiletine
* Moricizine
* Pilsicainide
* Prajmaline
* Procainamide
* Propafenone
* Quinidine
* Sparteine
* Tocainide

* Anticonvulsants: Acetylpheneturide
* Carbamazepine
* Cenobamate
* Chlorphenacemide
* Elpetrigine
* Eslicarbazepine acetate
* Ethotoin
* Fosphenytoin
* Lacosamide
* Licarbazepine
* Mephenytoin
* Oxcarbazepine
* Oxitriptyline
* Phenacemide
* Pheneturide
* Phenytoin
* Rufinamide
* Sipatrigine
* Topiramate
* Sodium valproate
* Valnoctamide
* Valproate pivoxil
* Valproate semisodium
* Valproic acid
* Valpromide
* Zonisamide

* Local anesthetics: pFBT
* Amylocaine
* Articaine
* Benzocaine
* Bupivacaine (Levobupivacaine, Ropivacaine)
* Butacaine
* Butamben
* Chloroprocaine
* Cinchocaine
* Cocaine
* Cyclomethycaine
* Dimethocaine
* Diphenhydramine
* Etidocaine
* Hexylcaine
* Iontocaine
* Lidocaine
* Mepivacaine
* Meprylcaine
* Metabutoxycaine
* Orthocaine
* Piperocaine
* Prilocaine
* Procaine
* Propoxycaine
* Proxymetacaine
* Risocaine
* Tetracaine
* Trimecaine

* Analgesics: AZD-3161
* DSP-2230
* Funapide
* GDC-0276
* NKTR-171
* PF-04531083
* PF-05089771
* Ralfinamide
* Raxatrigine
* RG7893 (GDC-0287)

* Toxins: Conotoxins
* Neosaxitoxin
* Saxitoxin
* Tetrodotoxin
* Zetekitoxin AB

* Others: Buprenorphine
* Evenamide
* Menthol (mint)
* Safinamide
* Tricyclic antidepressants

|

Activators|

* Aconitine
* Atracotoxins (ω-Atracotoxin, Robustoxin, Versutoxin)
* Batrachotoxin
* Ciguatoxins
* Grayanotoxins
* Poneratoxin

ENaC|

| Blockers|

* Amiloride
* Benzamil
* Triamterene

|

Activators|

* Solnatide

ASICs|

| Blockers|

* A-317567
* Amiloride
* Aspirin
* Ibuprofen
* PcTX1

|

Chloride|

| CaCCs|

| Blockers|

* Crofelemer
* DIDS
* Ethacrynic acid
* Flufenamic acid
* Fluoxetine
* Furosemide
* Glibenclamide
* Mefloquine
* Mibefradil
* Niflumic acid

|

Activators|

* Carbachol

CFTR|

| Blockers|

* Glibenclamide
* Lonidamine
* Piretanide

|

Activators|

* 1,7-Phenanthroline
* 1,10-Phenanthroline
* 4,7-Phenanthroline
* 7,8-Benzoquinoline
* Ivacaftor
* Phenanthridine

Unsorted|

| Blockers|

* Bumetanide
* Flufenamic acid
* Meclofenamic acid
* Mefenamic acid
* Mepacrine
* Niflumic acid
* Talniflumate
* Tolfenamic acid
* Trifluoperazine

|

Others|

| TRPs|

* See here instead.

|

LGICs|

* See here instead.

See also: Receptor/signaling modulators • Transient receptor potential channel modulators

* v
* t
* e

Progesterone receptor modulators

PR|

| Agonists|

* Progesterone derivatives: 3β-Dihydroprogesterone
* 5α-Dihydroprogesterone
* 9α-Bromo-11-ketoprogesterone
* 11-Dehydroprogesterone
* 11-Deoxycorticosterone
* 16α-Hydroxyprogesterone
* 20α-Dihydroprogesterone
* 20β-Dihydroprogesterone
* Dimepregnen
* Diosgenin
* P1-185
* Progesterone
* Progesterone 3-acetyl enol ether
* Quingestrone

* Retroprogesterone derivatives: 20α-Dihydrodydrogesterone
* 20α-Dihydrotrengestone
* DU-41164
* DU-41165
* Dydrogesterone
* Retroprogesterone
* Ro 6-3129
* Trengestone

* 17α-Substituted progesterone derivatives: 6α-Methyl-17α-bromoprogesterone
* 15β-Hydroxycyproterone acetate
* 16-Methylene-17α-hydroxyprogesterone acetate
* 17α-Bromoprogesterone
* 17α-Hydroxyprogesterone (hydroxyprogesterone)
* 17α-Methylprogesterone
* Acetomepregenol (mepregenol diacetate)
* Algestone
* Algestone acetonide
* Algestone acetophenide
* Anagestone
* Anagestone acetate
* Bromethenmadinone
* Bromethenmadinone acetate
* Butagest (buterol)
* Chlormadinone
* Chlormadinone acetate
* Chlormadinone caproate
* Chlormethenmadinone
* Chlormethenmadinone acetate
* Cismadinone
* Cismadinone acetate
* Clogestone
* Clogestone acetate
* Clomegestone
* Clomegestone acetate
* Cymegesolate
* Cyproterone acetate
* Delmadinone
* Delmadinone acetate
* Edogestrone
* Flugestone
* Flugestone acetate
* Fluorometholone
* Fluorometholone acetate
* Flumedroxone
* Flumedroxone acetate
* Fluoromedroxyprogesterone acetate
* Gestaclone
* Haloprogesterone
* Hydromadinone
* Hydromadinone acetate
* Hydroxyprogesterone acetate
* Hydroxyprogesterone caproate (hydroxyprogesterone hexanoate)
* Hydroxyprogesterone heptanoate (hydroxyprogesterone enanthate)
* Hydroxyprogesterone heptanoate benzilic acid hydrazone
* Mecigestone (pentarane B)
* Medrogestone
* Medroxyprogesterone
* Medroxyprogesterone acetate
* Medroxyprogesterone caproate
* Megestrol
* Megestrol acetate
* Megestrol caproate
* Melengestrol
* Melengestrol acetate
* Methenmadinone
* Methenmadinone acetate
* Methenmadinone caproate
* Mometasone
* Mometasone furoate
* Osaterone
* Osaterone acetate
* Pentagestrone
* Pentagestrone acetate
* Pentarane A
* Proligestone

* 19-Norprogesterone derivatives: 17α-Methyl-19-norprogesterone
* 18-Methylsegesterone acetate
* 19-Norprogesterone
* Amadinone
* Amadinone acetate
* Demegestone
* Fluoro ethyl norprogesterone
* Fluoro furanyl norprogesterone
* Gestadienol
* Gestadienol acetate
* Gestonorone acetate (gestronol acetate)
* Gestonorone caproate (gestronol hexanoate)
* Gestronol (gestonorone)
* Nomegestrol
* Nomegestrol acetate
* Norgestomet
* ORG-2058
* Oxogestone
* Oxogestone phenpropionate (xinogestone)
* Promegestone
* Segesterone
* Segesterone acetate (nestorone)
* Trimegestone

* Testosterone derivatives: Progestins: 6,6-Difluoronorethisterone
* 6,6-Difluoronorethisterone acetate
* 17α-Allyl-19-nortestosterone
* Allylestrenol
* Altrenogest
* Chloroethynylnorgestrel
* Cingestol
* Danazol
* Desogestrel
* Dienogest
* Ethisterone
* Ethynerone
* Etonogestrel
* Etynodiol
* Etynodiol diacetate
* Gestodene
* Gestrinone
* Levonorgestrel
* Levonorgestrel esters (e.g., levonorgestrel butanoate)
* Lynestrenol
* Lynestrenol phenylpropionate
* Metynodiol
* Metynodiol diacetate
* Norelgestromin
* Norethisterone (norethindrone)
* Norethisterone esters (e.g., norethisterone acetate, norethisterone enanthate)
* Noretynodrel
* Norgesterone
* Norgestimate
* Norgestrel
* Norgestrienone
* Norvinisterone
* Oxendolone
* Quingestanol
* Quingestanol acetate
* Tibolone
* Tigestol
* Tosagestin; Anabolic–androgenic steroids: 11β-Methyl-19-nortestosterone
* 11β-Methyl-19-nortestosterone dodecylcarbonate
* 19-Nor-5-androstenediol
* 19-Nor-5-androstenedione
* 19-Nordehydroepiandrosterone
* Bolandiol
* Bolandiol dipropionate
* Bolandione
* Dimethisterone
* Dienedione
* Dienolone
* Dimethandrolone
* Dimethandrolone buciclate
* Dimethandrolone dodecylcarbonate
* Dimethandrolone undecanoate
* Dimethyldienolone
* Dimethyltrienolone
* Ethyldienolone
* Ethylestrenol (ethylnandrol)
* Methyldienolone
* Metribolone (R-1881)
* Methoxydienone (methoxygonadiene)
* Mibolerone
* Nandrolone
* Nandrolone esters (e.g., nandrolone decanoate, nandrolone phenylpropionate)
* Norethandrolone
* Normethandrone (methylestrenolone, normethandrolone, normethisterone)
* RU-2309
* Tetrahydrogestrinone
* Trenbolone (trienolone)
* Trenbolone esters (e.g., trenbolone acetate, trenbolone enanthate)
* Trendione
* Trestolone
* Trestolone acetate

* Spirolactone derivatives: Canrenoic acid
* Canrenone
* Drospirenone
* Mespirenone
* Potassium canrenoate
* Prorenone
* SC-5233 (spirolactone)
* SC-8109
* Spironolactone
* Spirorenone

* Nonsteroidal: 3,8-Dihydrodiligustilide
* LG-2527
* LG-100128
* Riligustilide
* RWJ-26819
* RWJ-49853
* RWJ-60130
* Tanaproget
* ZM-182345

* Unknown: ORG-47241
* ORG-201745

|

Mixed
(SPRMs)|

* Steroidal: Dihydroethisterone
* 5α-Dihydrolevonorgestrel
* 5α-Dihydronorethisterone
* Asoprisnil
* Asoprisnil ecamate
* Guggulsterone
* J1042
* LG-120838
* Metapristone (RU-42633)
* Mifepristone (RU-486)
* ORF-9371
* ORF-9326
* ORG-31710
* ORG-33628
* RMI-12936
* Telapristone
* Ulipristal acetate
* Vilaprisan
* ZK-137316

* Nonsteroidal: Apigenin
* Kaempferol
* LG-120920
* Naringenin
* PRA-910
* Syringic acid

Antagonists|

* Steroidal: Aglepristone
* Lilopristone
* Lonaprisan
* Onapristone
* ORG-31710
* ORG-31806
* ORG-33628
* RTI 3021–022
* Toripristone
* Zanoterone

* Nonsteroidal: Darolutamide
* LG-001447
* LG-100127
* LG-100128
* LG-120830
* LG-121046
* Valproic acid
* ZM-150271
* ZM-172406

mPR
(PAQR)|

| Agonists|

* 5α-Dihydroprogesterone
* 5β-Dihydroprogesterone
* 11-Deoxycortisone (21-hydroxyprogesterone)
* 11-Deoxycortisol (17α,21-dihydroxyprogesterone)
* 17α-Hydroxyprogesterone
* Allopregnanolone
* Mifepristone
* Pregnenolone
* Progesterone

|

Antagonists|

* Mifepristone

See also
Receptor/signaling modulators
Progestogens and antiprogestogens
Androgen receptor modulators
Estrogen receptor modulators
List of progestogens

* v
* t
* e

Xenobiotic-sensing receptor modulators

CAR|

* Agonists: 6,7-Dimethylesculetin
* Amiodarone
* Artemisinin
* Benfuracarb
* Carbamazepine
* Carvedilol
* Chlorpromazine
* Chrysin
* CITCO
* Clotrimazole
* Cyclophosphamide
* Cypermethrin
* DHEA (prasterone)
* Efavirenz
* Ellagic acid
* Griseofulvin
* Methoxychlor
* Mifepristone
* Nefazodone
* Nevirapine
* Nicardipine
* Octicizer
* Permethrin
* Phenobarbital
* Phenytoin
* Pregnanedione (5β-dihydroprogesterone)
* Reserpine
* TCPOBOP
* Telmisartan
* Tolnaftate
* Troglitazone
* Valproic acid

* Antagonists: 3,17β-Estradiol
* 3α-Androstanol
* 3α-Androstenol
* 3β-Androstanol
* 17-Androstanol
* AITC
* Ethinylestradiol
* Meclizine
* Nigramide J
* Okadaic acid
* PK-11195
* S-07662
* T-0901317

PXR|

* Agonists: 17α-Hydroxypregnenolone
* 17α-Hydroxyprogesterone
* Δ4-Androstenedione
* Δ5-Androstenediol
* Δ5-Androstenedione
* AA-861
* Allopregnanediol
* Allopregnanedione (5α-dihydroprogesterone)
* Allopregnanolone (brexanolone)
* Alpha-Lipoic acid
* Ambrisentan
* AMI-193
* Amlodipine besylate
* Antimycotics
* Artemisinin
* Aurothioglucose
* Bile acids
* Bithionol
* Bosentan
* Bumecaine
* Cafestol
* Cephaloridine
* Cephradine
* Chlorpromazine
* Ciglitazone
* Clindamycin
* Clofenvinfos
* Chloroxine
* Clotrimazole
* Colforsin
* Corticosterone
* Cyclophosphamide
* Cyproterone acetate
* Demecolcine
* Dexamethasone
* DHEA (prasterone)
* DHEA-S (prasterone sulfate)
* Dibunate sodium
* Diclazuril
* Dicloxacillin
* Dimercaprol
* Dinaline
* Docetaxel
* Docusate calcium
* Dodecylbenzenesulfonic acid
* Dronabinol
* Droxidopa
* Eburnamonine
* Ecopipam
* Enzacamene
* Epothilone B
* Erythromycin
* Famprofazone
* Febantel
* Felodipine
* Fenbendazole
* Fentanyl
* Flucloxacillin
* Fluorometholone
* Griseofulvin
* Guggulsterone
* Haloprogin
* Hetacillin potassium
* Hyperforin
* Hypericum perforatum (St John's wort)
* Indinavir sulfate
* Lasalocid sodium
* Levothyroxine
* Linolenic acid
* LOE-908
* Loratadine
* Lovastatin
* Meclizine
* Metacycline
* Methylprednisolone
* Metyrapone
* Mevastatin
* Mifepristone
* Nafcillin
* Nicardipine
* Nicotine
* Nifedipine
* Nilvadipine
* Nisoldipine
* Norelgestromin
* Omeprazole
* Orlistat
* Oxatomide
* Paclitaxel
* Phenobarbital
* Piperine
* Plicamycin
* Prednisolone
* Pregnanediol
* Pregnanedione (5β-dihydroprogesterone)
* Pregnanolone
* Pregnenolone
* Pregnenolone 16α-carbonitrile
* Proadifen
* Progesterone
* Quingestrone
* Reserpine
* Reverse triiodothyronine
* Rifampicin
* Rifaximin
* Rimexolone
* Riodipine
* Ritonavir
* Simvastatin
* Sirolimus
* Spironolactone
* Spiroxatrine
* SR-12813
* Suberoylanilide
* Sulfisoxazole
* Suramin
* Tacrolimus
* Tenylidone
* Terconazole
* Testosterone isocaproate
* Tetracycline
* Thiamylal sodium
* Thiothixene
* Thonzonium bromide
* Tianeptine
* Troglitazone
* Troleandomycin
* Tropanyl 3,5-dimethulbenzoate
* Zafirlukast
* Zeranol

* Antagonists: Ketoconazole
* Sesamin

See also
Receptor/signaling modulators
Nuclear receptor modulators

*[INN]: International nonproprietary name
*[US]: United States
*[AU]: Australia
*[CA]: Canada
*[UK]: United Kingdom
*[CID]: Compound ID
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[AR]: Androgen receptor
*[SARMs]: Selective androgen receptor modulator
*[GPRC6A]: G protein-coupled receptor family C group 6 member A
*[VDCCs]: Voltage-dependent calcium channels
*[VGKCs]: Voltage-gated potassium channels
*[IRKs]: Inwardly rectifying potassium channel
*[KATP]: ATP-sensitive potassium channel
*[GIRK]: G protein-coupled inwardly-rectifying potassium channel
*[KCa]: Calcium-activated potassium channel
*[K2Ps]: Tandem pore domain potassium channel
*[VGSCs]: Voltage-gated sodium channels
*[ENaC]: Epithelial sodium channel
*[ASICs]: Acid-sensing ion channel
*[CaCCs]: Calcium-activated chloride channel
*[CFTR]: Cystic fibrosis transmembrane conductance regulator
*[TRPs]: Transient receptor potential channels
*[LGICs]: Ligand gated ion channels
*[PR]: Progesterone receptor
*[SPRMs]: Selective progesterone receptor modulators
*[mPR]: Membrane progesterone receptor
*[PAQR]: Progestin and adipoQ receptor
*[CAR]: Constitutive androstane receptor
*[PXR]: Pregnane X receptor