N-(p-Amylcinnamoyl)anthranilic acid

Names
Preferred IUPAC name

2-[(2E)-3-(4-Pentylphenyl)prop-2-enamido]benzoic acid

Other names

* N-(4-Pentylcinnamoyl)anthranilic acid
* 4-Amylcinnamoylanthranilic acid
* p-Amylcinnamoylanthranilic acid
* ACA
* ACAA

Identifiers

CAS Number

* 99196-74-4
* 110683-10-8 (non-specific) Y

3D model (JSmol)

* Interactive image

ChEBI |

* CHEBI:139349

ChEMBL |

* ChEMBL173443

ChemSpider |

* 4510067

ECHA InfoCard | 100.189.123
EC Number |

* 662-753-7

IUPHAR/BPS

* 2443

PubChem CID

* 5353376

UNII |

* LCJ9M6AJ5F Y

CompTox Dashboard (EPA)

* DTXSID401166445

InChI

* InChI=1S/C21H23NO3/c1-2-3-4-7-16-10-12-17(13-11-16)14-15-20(23)22-19-9-6-5-8-18(19)21(24)25/h5-6,8-15H,2-4,7H2,1H3,(H,22,23)(H,24,25)/b15-14+

Key: GAMRBCZMOOMBSQ-CCEZHUSRSA-N

SMILES

* CCCCCC1=CC=C(C=C1)/C=C/C(=O)NC2=CC=CC=C2C(=O)O

Properties

Chemical formula

| C21H23NO3
Molar mass | 337.419 g·mol−1
Appearance  | White to off-white powder[1]
Hazards
GHS labelling:[1]

Pictograms

Signal word

| Warning

Hazard statements

| H410

Precautionary statements

| P273, P391, P501

Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Infobox references

Chemical compound

N-(p-Amylcinnamoyl)anthranilic acid (ACA) is a modulator of various ion channels in the heart. ACA is an effective reversible inhibitor of calcium-activated chloride channels and, to a lesser extent, cAMP-activated chloride channels, without affecting L-type calcium channels.[2] Calcium-activated chloride channels are believed to be involved in developing arrhythmia.[2][3]

## Arrhythmia

[edit]

Arrhythmia is a cardiac disease which is characterized by an irregular heartbeat. Some forms of arrhythmia are dangerous and life-threatening, while others are comparably minor. Heart cells (cardiac myocytes) contract due to an increase in the charge across the membrane (depolarization), which generates an action potential. Irregular contractions can cause arrhythmia to occur.[3][4]

## Calcium-activated chloride channels

[edit]

The calcium-activated chloride channel is present in cardiac myocytes of many species, such as rabbit[5][6] and pig,[2][7] but their presence in human cardiac myocytes is under debate. Some have provided evidence that these channels are present in human atrial cells,[8] while others have failed to find similar results.[9]

The calcium-activated chloride channel is an important component in the early phase of repolarization (bringing the charge across the membrane back to normal) of cardiac muscle cells,[10] contributing to the plateau formation during an action potential.[7] While the heart is at rest, the chloride channel current can be activated, causing an outward flow of chloride, inducing a depolarizing current. This current is generally large enough to generate an action potential, called a delayed after-depolarization. Delayed after-depolarizations can lead to arrhythmias.[3][11] Since the chloride channel is bound and activated by calcium, this tends to occur more often in cells that are already under calcium stress.[11] The calcium-activated chloride current is also doubled when stimulated by the sympathetic nervous system, likely due to an increase in calcium release, although the channel could potentially be under a direct control by the sympathetic nervous system.[3]

## Treatment of arrhythmia

[edit]

Due to the ability of the calcium-activated chloride channel to generate arrhythmias, blockage of the channel may result in antiarrythmogenic action. Blocking the calcium current reduces delayed after-depolarization amplitudes enough to prevent generation of an action potential.[3] ACA has been shown to inhibit the calcium-activated chloride current, but this effect is reversible upon removal of the drug. ACA may also inhibit hyperpolarization of the cell, prolonging the action potential. ACA has potential as an antiarrhythmogenic treatment,[2][3] as well as a tool to further study chloride channels.[2]

## References

[edit]

1. ^ "N-(p-Amylcinnamoyl)anthranilic acid". Sigma-Aldrich.
2. ^ a b c d e Gwanyanya A, Macianskiene R, Bito V, Sipido KR, Vereecke J, Mubagwa K. "Inhibition of the calcium-activated chloride current in cardiac ventricular myocytes by N-(p-amylcinnamoyl)anthranilic acid (ACA)". Biochem Biophys Res Commun 2010;402:531–536.
3. ^ a b c d e f Verkerk A, Veldkamp M, Bouman L, van Ginneken A. "Calcium-Activated Cl− Current Contributes to Delayed After depolarizations in Single Purkinje and Ventricular Myocytes". Circulation 2000;101:2639–2644.
4. ^ Guyton A, Hall J. Textbook of Medical Physiology, Tenth Ed. Philadelphia, PA:W.B. Saunders Company, 2000.
5. ^ Zygmunt AC, Gibbons WR. "Calcium-activated chloride current in rabbit ventricular myocytes". Circ Res 1991:68:424–437.
6. ^ Sipido KR, Callewaert G, Carmeliet E. "[Ca2+]i transients and [Ca2+]i-dependent chloride current in single Purkinje cells from rabbit heart". J Physiol 1993;468:641–667.
7. ^ a b Li GR, Du XL, Siow YL, O K, Tse HF, Lau CP. "Calcium-activated transient outward chloride current and phase 1 repolarization of swine ventricular action potential". Cardiovasc Res 2003;58:89–98.
8. ^ Escande D, Coulombe A, Faivre JF, Deroubaix E, Coraboeuf E. "Two types of transient outward currents in adult human atrial cells". Am J Physiol 1987;252:H143–H148.
9. ^ Li GR, Feng J, Wang Z, Fermini B, Nattel S. "Comparative mechanisms of 4-aminopyridine-resistant Ito in human and rabbit atrial myocytes". Am J Physiol 1995;269:H463–H472.
10. ^ Kenyon JL, Gibbons WR. "4-Aminopyridine and the early outward current of sheep cardiac Purkinje fibers". J Gen Physiol 1979;73:139–157.
11. ^ a b Zygmunt AC, Goodrow RJ, Weigel CM. "INaCa and ICl(Ca) contribute to isoproterenol-induced delayed after depolarizations in midmyocardial cells". Am J Physiol 1998;275:H1979–H1992.

* v
* t
* e

Ion channel modulators

Calcium|

| VDCCsTooltip Voltage-dependent calcium channels|

| 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|

| VGKCsTooltip Voltage-gated potassium channels|

| 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

IRKsTooltip Inwardly rectifying potassium channel|

| Blockers|

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

* GIRKTooltip G protein-coupled inwardly rectifying potassium channel-specific: Barium
* Caramiphen
* Cloperastine
* Clozapine
* Dextromethorphan
* Ethosuximide
* Ifenprodil
* Tertiapin
* Tipepidine

|

Activators|

* KATPTooltip ATP-sensitive potassium channel-specific: Aprikalim
* Bimakalim
* Cromakalim
* Diazoxide
* Emakalim
* Levcromakalim
* Mazokalim
* Minoxidil
* Minoxidil sulfate
* Naminidil
* Nicorandil
* Pinacidil
* Rilmakalim
* Sarakalim

* GIRKTooltip G protein-coupled inwardly rectifying potassium channel-specific: ML-297 (VU0456810)

KCaTooltip Calcium-activated potassium channel|

| Blockers|

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

|

Activators|

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

K2PsTooltip Tandem pore domain potassium channel|

| Blockers|

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

|

Activators|

* Riluzole

Sodium|

| VGSCsTooltip Voltage-gated sodium channels|

| 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
* Lamotrigine
* 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)
* Suzetrigine

* 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

ENaCTooltip Epithelial sodium channel|

| Blockers|

* Amiloride
* Benzamil
* Triamterene

|

Activators|

* Solnatide

ASICsTooltip Acid-sensing ion channel|

| Blockers|

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

|

Chloride|

| CaCCsTooltip Calcium-activated chloride channel|

| Blockers|

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

|

Activators|

* Carbachol

CFTRTooltip Cystic fibrosis transmembrane conductance regulator|

| 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|

| TRPsTooltip Transient receptor potential channels|

* See here instead.

|

LGICsTooltip Ligand gated ion channels|

* See here instead.

See also: Receptor/signaling modulators • Transient receptor potential channel modulators
*[CID]: Compound ID
*[EPA]: U.S. Environmental Protection Agency
*[H410]: H410: Very toxic to aquatic life with long lasting effects
*[P273]: P273: Avoid release to the environment.
*[P391]: P391: Collect spillage.
*[P501]: P501: Dispose of contents/container to ...
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[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