List of investigational analgesics

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This is a list of investigational analgesics, or analgesics that are currently under development for clinical use but are not yet approved. Chemical/generic names are listed first, with developmental code names, synonyms, and brand names in parentheses.

## Opioid receptor modulators

[edit]

* Axelopran/oxycodone – combination of a centrally active μ-opioid receptor agonist and a peripherally selective μ-, κ-, and δ-opioid receptor antagonist.[1]
* Cebranopadol (GRT-6005) – non-selective μ-opioid receptor, nociceptin receptor, and δ-opioid receptor full agonist and κ-opioid receptor partial agonist[2]
* Desmetramadol (O-desmethyltramadol; Omnitram) – μ-opioid receptor agonist, norepinephrine reuptake inhibitor (NRI), and 5-HT2C receptor antagonist.[3]
* Lexanopadol (GRT-6006, GRT13106G) – non-selective opioid receptor agonist[4]
* Oxycodone/naltrexone – combination of a μ-opioid receptor agonist and a μ- and κ-opioid receptor antagonist.[5]

## Sodium channel blockers

[edit]

* BIIB-095 – state-dependent and use-dependent Nav blocker, including Nav1.7.[6]
* CC-8464 (ASP-1807) – selective Nav1.7 blocker[7]
* Cenobamate (YKP-3089) – atypical voltage-gated sodium channel blocker.[8][9]: 5593–5605 [10]
* DSP-2230 – selective Nav1.7 and Nav1.8 blocker.[11]
* Funapide (TV-45070, XEN402) – selective Nav1.7 and Nav1.8 blocker.[12]
* GDC-0276 (RG-7893) – selective Nav1.7 blocker [1]
* GDC-0310 (RG-6029) – selective Nav1.7 blocker [2]
* NKTR-171 – voltage-gated sodium channel blocker [3]
* PF-05089771 – selective Nav1.7 and Nav1.8 blocker [4]
* Ralfinamide (NW-1029) – non-selective voltage-gated sodium channel blocker, as well as other actions [5]
* Tetrodotoxin (9401-TTX; Tectin, Tetrodin, Tocudin) – non-selective voltage-gated sodium channel blocker [6]
* Vixotrigine (formerly raxatrigine; CNV1014802, GSK-1014802, BIIB 074) – non-selective voltage-gated sodium channel blocker [7][citation needed]
* VX-150 – selective Nav1.8 blocker [8]
* VX-548 – selective Nav1.8 blocker[13][14]

## Calcium channel blockers

[edit]

* HSK16149 - selective ligand of α2δ subunit of voltage-gated calcium channel [9]

## TRP channel modulators

[edit]

* Capsaicin (Adlea, ALGRX-4975, CNTX-4975, VLNX-4975) – TRPV1 agonist [10]
* Capsaicin/diclofenac – combination of a TRPV1 agonist and a COX-2 inhibitor for topical application [11]
* CMX-020 – TRPV1 modulator as well as CB1 and CB2 receptor modulator [12]
* DWP-05195 (TR-1) – TRPV1 antagonist [13]
* GRC-6211 – TRPV1 agonist [14]
* JNJ-38893777 – TRPV1 antagonist [15]
* Mavatrep (JNJ‐39439335) – TRPV1 antagonist.[15]: 712–726 [16]
* NEO-6860 – TRPV1 antagonist [16]
* Parentide (DD-04107) – TRPV1 antagonist [17]
* Resiniferatoxin (RTX; MCP-101) – TRPV1 agonist [18]
* SAR-115740 – TRPV1 antagonist [19]
* Tivanisiran (SYL-1001) – TRPV1 antagonist [20]

## Cannabinoid receptor modulators

[edit]

* ABX-1431 – selective monoacylglycerol lipase inhibitor[21]
* Cannabidiol (CBD) – cannabinoid receptor modulator [22][23]
* Cannabidivarin (CBDV; GWP-42006) – cannabinoid receptor modulator [24]
* CMX-020 – TRPV1 modulator as well as CB1 and CB2 receptor modulator [25]
* Dronabinol (Δ9-THC; ECP022A, Namisol) – CB1 and CB2 receptor agonist [26][27]
* Nabilone – CB1 and CB2 receptor agonist [28]
* NEO-1940 – CB1 and CB2 receptor agonist [29]
* Olorinab (APD-371) – CB2 receptor agonist [30]

## Nerve growth factor inhibitors

[edit]

* Fasinumab (REGN-475, SAR-164877) – monoclonal antibody against nerve growth factor[31]
* Fulranumab (AMG-403, JNJ-42160443) – monoclonal antibody against nerve growth factor [32]
* GBR-900 – monoclonal antibody against TrkA[33]
* GZ-389988 – TrkA, TrkB, and TrkC kinase inhibitor[34]
* LEVI-04 (p75NTR-Fc) – LNGF receptor (p75NTR) fusion protein and decoy receptor for nerve growth factor [35]
* NRD135S-E1 – tyrosine kinase modulator[36][37]
* ONO-4474 – peripherally selective TrkA, TrkB, and TrkC kinase inhibitor[38]
* Ranevetmab (NV-01) – monoclonal antibody against nerve growth factor for dogs [39]
* Tanezumab (PF-4383119, RI-624, RN-624) – monoclonal antibody against nerve growth factor [40]
* VM-902A – selective, peripherally selective allosteric inhibitor of TrkA [41]

## Others

[edit]

* ALLOD-2 – undefined mechanism of action [42]
* CR-4056 – imidazoline I2 receptor agonist [43]
* E-52862 (MR-309; S1A; S1RA) – sigma-1 receptor antagonist [44]
* HSP-3150 – undefined mechanism of action [45]
* KCP-506 – nicotinic acetylcholine receptor antagonist [46]
* LATER – CRISPR-dCas9 gene-editing[17]
* PAX-01 – undefined mechanism of action [47]

## See also

[edit]

* List of investigational drugs

## References

[edit]

1. ^ "Drug profile | Axelopran/oxycodone". AdisInsight. Theravance Biopharma. 1 October 2021. Retrieved 29 October 2022.
2. ^ "Drug profile | Cebranopadol". AdisInsight. Tris Pharma. 14 August 2022. Retrieved 29 October 2022.
3. ^ "Drug profile | Desmetramadol". AdisInsight. Syntrix Biosystems. 5 October 2021. Retrieved 2 November 2022.
4. ^ "Drug profile | Lexanopadol". AdisInsight. 20 August 2018. Archived from the original on 25 December 2018. Retrieved 2 November 2022.
5. ^ "Drug profile | Oxycodone/naltrexone". AdisInsight. Elite Pharmaceuticals. 16 April 2021. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
6. ^ "Drug profile | BIIB 095". AdisInsight. Biogen. 7 May 2021. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
7. ^ Drug profile | CC 8464. Chromocell Corporation. 28 November 2019. Archived from the original on 15 March 2022. Retrieved 14 November 2022. `{{cite book}}`: `|work=` ignored (help)
8. ^ "Drug profile | Cenobamate". AdisInsight. SK biopharmaceuticals. 28 November 2019. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
9. ^ Zaccara, Gaetano; Schmidt, D. (2017). "Antiepileptic Drugs in Clinical Development: Differentiate or Die?". Current Pharmaceutical Design. 23 (37). Bentham Science Publishers: 5593–5605. doi:10.2174/1381612823666170809100524. eISSN 1873-4286. ISSN 1381-6128. PMID 28799516. S2CID 3676340.
10. ^ Nakamura, Michiko; Shin, Hyewon; Jang, Il-Sung (26 April 2018). "Mechanism of Action of Cenobamate: Preferential Inhibition of the Persistent Sodium Current (P5.278)". Neurology. 90 (15 Supplement). doi:10.1212/WNL.90.15_supplement.P5.278. eISSN 1526-632X. ISSN 0028-3878. LCCN 55043902. OCLC 960771045. S2CID 80887455.
11. ^ "Drug profile | DSP 2230". AdisInsight. Sumitomo Dainippon Pharma. 4 April 2022. Archived from the original on 14 November 2022. Retrieved 14 November 2022.
12. ^ Drug profile | Funapide. Xenon Pharmaceuticals. 6 September 2022. Archived from the original on 14 November 2022. Retrieved 14 November 2022. `{{cite book}}`: `|work=` ignored (help)
13. ^ Nichols, Heather (19 July 2021). "Vertex Initiates Phase 2 Clinical Trial Program for VX-548 for the Treatment of Acute Pain". Vertex Pharmaceuticals (Press Release). Retrieved 14 November 2022. "Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced that it has begun a Phase 2 proof-of-concept (POC) study in acute pain following bunionectomy surgery with the selective NaV1.8 inhibitor VX-548 and that it expects to commence a second Phase 2 study in acute pain following abdominoplasty surgery in the coming weeks."
14. ^ Cross, Ryan (31 March 2022). "Vertex's non-opioid painkiller shows promise in people recovering from surgery". The Boston Globe. ISSN 0743-1791. OCLC 66652431. Archived from the original on 19 May 2022. Retrieved 14 November 2022. ""There is an enormous need for novel non-opioid analgesics with no abuse liability," and Vertex's results are an "important advance," said Dr. Clifford J. Woolf, director of the F.M. Kirby Neurobiology Center and Boston Children's Hospital. It will be important for Vertex to determine whether the drug also works for patients with chronic pain, such as diabetic neuropathy and low back pain, "where the clinical need is highest," he added."
15. ^ Manitpisitkul, Prasarn; Shalayda, Kevin; Russell, Lucille; Sanga, Panna; Solanki, Bhavna; Caruso, Joseph; Iwaki, Yuki; Moyer, John A. (10 November 2017). "Pharmacokinetics and Safety of Mavatrep (JNJ-39439335), a TRPV1 Antagonist in Healthy Japanese and Caucasian Men: A Double-Blind, Randomized, Placebo-Controlled, Sequential-Group Phase 1 Study". Clinical Pharmacology in Drug Development. 7 (7): 712–726. doi:10.1002/cpdd.413. eISSN 2160-7648. ISSN 2160-763X. PMID 29125703. S2CID 11755963.
16. ^ Manitpisitkul, Prasarn; Shalayda, Kevin; Russell, Lucille; Sanga, Panna; Williams, Yinka; Solanki, Bhavna; Caruso, Joseph; Moyer, John A. (2018). "Bioavailability and Pharmacokinetics of TRPV1 Antagonist Mavatrep (JNJ-39439335) Tablet and Capsule Formulations in Healthy Men: Two Open-Label, Crossover, Single-Dose Phase 1 Studies". Clinical Pharmacology in Drug Development. 7 (7): 699–711. doi:10.1002/cpdd.412. ISSN 2160-7648. PMID 29125700. S2CID 32666782.
17. ^ Moreno, Ana M.; Alemán, Fernando; Catroli, Glaucilene F.; Hunt, Matthew; Hu, Michael; et al. (10 March 2021). "Long-lasting analgesia via targeted in situ repression of NaV1.7 in mice". Science Translational Medicine. 13 (584). doi:10.1126/scitranslmed.aay9056. eISSN 1946-6242. ISSN 1946-6234. PMC 8830379. PMID 33692134.

## External links

[edit]

* AdisInsight - Springer

* v
* t
* e

Analgesics (N02A, N02B)

Opioids|

| Opiates/opium|

* Codeine#
* +aspirin
* +paracetamol
* Morphine# (+naltrexone)
* Opium
* Laudanum
* Paregoric

|

Semisynthetic|

* Acetyldihydrocodeine
* Benzylmorphine
* Buprenorphine (+naloxone)
* Butorphanol
* Desomorphine
* Diamorphine (heroin)
* Dihydrocodeine (+paracetamol)
* Dihydromorphine
* Etorphine
* Ethylmorphine
* Hydrocodone (+paracetamol, +ibuprofen, +aspirin)
* Hydromorphinol
* Hydromorphone
* Levorphanol
* Metopon
* Nalbuphine
* Nicocodeine
* Nicodicodine
* Nicomorphine
* Oxycodone (+paracetamol, +aspirin, +ibuprofen, +naloxone, +naltrexone)
* Oxymorphone
* Papaveretum
* Thebacon

Synthetic|

* Alfentanil
* Alphaprodine
* Anileridine
* Bezitramide
* Carfentanil
* Dextromoramide
* Dextropropoxyphene
* Dezocine
* Dimenoxadol
* Dipipanone
* Ethoheptazine
* Fentanyl# (+fluanisone)
* Ketobemidone
* Lofentanil
* Meptazinol
* Methadone#
* NFEPP
* Norpipanone
* Oliceridine
* Pentazocine
* Pethidine (meperidine)
* Phenadoxone
* Phenazocine
* Phenoperidine
* Piminodine
* Piritramide
* Proheptazine
* Propiram
* Remifentanil
* Sufentanil
* Tapentadol
* Tilidine
* Tramadol (+celecoxib, +paracetamol)
* Viminol

Paracetamol-type|

* Acetanilide‡
* Bucetin‡
* Butacetin‡
* Paracetamol (acetaminophen)#
* +aspirin/caffeine
* +codeine
* +hydrocodone
* +ibuprofen
* +metoclopramide
* +oxycodone
* +propyphenazone/caffeine
* +tramadol
* Parapropamol‡
* Phenacetin‡
* Propacetamol‡

NSAIDs|

| Propionates|

* Benoxaprofen ‡
* Fenoprofen
* Flurbiprofen
* Ibuprofen# (Dexibuprofen) (+paracetamol)
* Ketoprofen (Dexketoprofen)
* Loxoprofen
* Naproxen
* Oxaprozin
* Suprofen
* Tiaprofenic acid
* Zaltoprofen

|

Oxicams|

* Isoxicam
* Lornoxicam
* Meloxicam
* Piroxicam
* Tenoxicam

Acetates|

* Acemetacin
* Bromfenac
* Diclofenac
* Etodolac
* Indometacin (Indometacin farnesil)
* Ketorolac
* Sulindac
* Tolmetin
* Zomepirac ‡

COX-2 inhibitors|

* Celecoxib (+tramadol)
* Etoricoxib
* Lumiracoxib ‡
* Parecoxib
* Rofecoxib ‡
* Valdecoxib ‡

Fenamates|

* Flufenamic acid
* Meclofenamic acid
* Mefenamic acid
* Tolfenamic acid

Salicylates|

* Aspirin (acetylsalicylic acid)# (+paracetamol/caffeine)
* Aloxiprin
* Benorylate
* Carbasalate calcium
* Choline salicylate
* Diflunisal
* Dipyrocetyl
* Ethenzamide
* Guacetisal
* Imidazole salicylate
* Magnesium salicylate
* Morpholine salicylate
* Potassium salicylate
* Salicin
* Salicylamide
* Salsalate
* Sodium salicylate
* Wintergreen (methyl salicylate)

Pyrazolones|

* Aminophenazone‡
* Ampyrone
* Metamizole (dipyrone)
* Nifenazone
* Phenazone
* Propyphenazone (+paracetamol/caffeine)

Others|

* Benzydamine
* Floctafenine
* Glafenine
* Nabumetone
* Nimesulide
* Proquazone

Cannabinoids|

* Cannabidiol
* Cannabis
* Nabilone
* Nabiximols
* Tetrahydrocannabinol (dronabinol)

Ion channel
modulators|

| Calcium blockers|

* Alcohol (ethanol)
* Gabapentin
* Gabapentin enacarbil
* Leconotide
* Mirogabalin
* Pregabalin
* Ziconotide

|

Sodium blockers|

* Carbamazepine
* Lacosamide
* Local anesthetics (e.g., cocaine, lidocaine)
* Mexiletine
* Nefopam
* Tricyclic antidepressants (e.g., amitriptyline#)

* Nav1.7/1.8-selective: DSP-2230§
* Funapide§
* PF-05089771§

Potassium openers|

* Flupirtine‡

Myorelaxants|

* Carisoprodol
* Chlorzoxazone
* Cyclobenzaprine
* Mephenoxalone
* Methocarbamol
* Orphenadrine

Others|

* Analgecine
* Analgesic adjuvant
* Bedinvetmab
* Camphor
* Capsaicin
* Clonidine
* Frunevetmab
* Ketamine
* Menthol
* Methoxyflurane
* Phenazopyridine
* Proglumide
* Rimazolium
* Tanezumab

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

* v
* t
* e

Neuropathic pain and fibromyalgia pharmacotherapies

Monoaminergics|

* SNRIsTooltip Serotonin–norepinephrine reuptake inhibitor (e.g., duloxetine, milnacipran)
* TCAsTooltip Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, dosulepin)
* Opioid MRIsTooltip monoamine reuptake inhibitors (e.g., tapentadol, tramadol)

Ion channel blockers|

* Anticonvulsants (e.g., gabapentin, pregabalin, mirogabalin, carbamazepine, oxcarbazepine, lacosamide, lamotrigine)
* Local anesthetics (e.g., lidocaine)
* Mexiletine
* TCAsTooltip Tricyclic antidepressants (e.g., amitriptyline, nortriptyline, desipramine)
* Ziconotide

Others|

* Alpha lipoic acid
* Benfotiamine
* Botulinum toxin A
* Bupropion
* Cannabinoids (e.g., cannabis, dronabinol, nabilone)
* NMDA receptor antagonists (e.g., ketamine, dextromethorphan, methadone)
* Opioids (e.g., hydrocodone, morphine, oxycodone, methadone, buprenorphine, tramadol, tapentadol)
* Sodium oxybate (GHB)

*[TRP]: Transient receptor potential
*[THC]: tetrahydrocannabinol
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid