Therapeutic Targets Database
BIDD Pharmainformatics Databases


TTD Target ID: TTDS00141

Target Information
NameNeuronal acetylcholine receptor protein, alpha-4 chain    
Type of targetSuccessful target    
SynonymsAlpha-4 nAChR    
Nicotinic acetylcholine receptor alpha4    
DiseaseAlzheimer's disease
[ICD9: 331.0   ICD10: G30]
[ICD9: 338   ICD10: R52]
Drug dependence
[ICD9: 303-304   ICD10: F10.2-F19.2]
Frontal lobe epilepsy
[ICD9: 345   ICD10: G40]
Neurodegenerative diseases
[ICD9: 330-337   ICD10: G30-G32]
[ICD9: 338,780   ICD10: R52, G89]
TrimethaphanApprovedHypertensive emergencies[6]
VareniclineApprovedSmoking cessation[7][8]
AZD1446Phase II completedCancer and Alzheimer's disease[9]
IsproniclinePhase II completedSchizophrenia; Alzheimer's Disease[10]
TC-5619Phase I/IIADHD[10]
IsproniclinePhase I completedAlzheimer's Disease; Cognitive disorder in schizophrenia[10]
ABT-894Discontinued in Phase II completedNeuropathic pain[11][12]
BioChemical ClassIon transport    
UniProt IDP43681
PDB Structure2GVT; 2LLY.    
FunctionAfter binding acetylcholine, the achr responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.    
Target ValidationClick to Find Target Validation Information.    
Inhibitor (2S,3S)-2-[13]
3-[2- (N,N,N-trimethylammonium)ethoxy]pyridine[14]
4- (4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one[15]
N,N-dimethyl (pyridin-3-yl)methanamine[19]
N,N-dimethyl-2- (pyridin-3-yloxy)ethanamine[19]
N,N-dimethyl-4- (pyridin-3-yl)but-3-yn-1-amine[19]
N-ethyl-N-methyl-4- (pyridin-3-yl)but-3-yn-1-amine[19]
N-methyl-2- (pyridin-3-yloxy)ethanamine[19]
N-methyl-4- (pyridin-3-yl)but-3-yn-1-amine[19]
N-methyl-N- (pyridin-3-ylmethyl)ethanamine[19]
N-methyllaurotetanine methiodide[17]
boldine methiodide[17]
glaucine methiodide[17]
predicentrine methiodide[17]
Barbituric acid derivative[20]
BinderNicotine replacement[3]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole (ABT 418): a novel cholinergic ligand with cognition-enhancing and anxiolytic activities: II. In vivo characterization. J Pharmacol Exp Ther. 1994 Jul;270(1):319-28. To Reference
Ref 2Challenges in Analgesic Drug Development. Clin Pharmacol Ther. 2009 Aug 12. To Reference
Ref 3Nicotine dependence--mechanisms and therapeutic strategies. Biochem Soc Symp. 1993;59:83-95. To Reference
Ref 4The nicotinic acetylcholine receptor agonist ABT-594 increases FGF-2 expression in various rat brain regions. Neuroreport. 1999 Dec 16;10(18):3909-13. To Reference
Ref 5Nicotinic and nonnicotinic receptor-mediated actions of vinblastine. Proc Soc Exp Biol Med. 1993 Jul;203(3):372-6. To Reference
Ref 6Mechanism of long-lasting block of ganglion nicotinic receptors by mono-ammonium compounds with long aliphatic chain. J Auton Nerv Syst. 1994 Aug;48(3):231-40. To Reference
Ref 7Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, selectively decreases ethanol consumption and seeking. Proc Natl Acad Sci U S A. 2007 Jul 24;104(30):12518-23. Epub 2007 Jul 11. To Reference
Ref 8Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation. Trends Pharmacol Sci. 2007 Jul;28(7):316-25. Epub 2007 Jun 18. To Reference
Ref 9Genentech. Product Development Pipeline. July 2009. To Reference
Ref 10AstraZeneca. Product Development Pipeline. January 29 2009. To Reference
Ref 11Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26. To Reference
Ref 12Modulators of nicotinic acetylcholine receptors as analgesics. Curr Opin Investig Drugs. 2004 Jan;5(1):76-81. To Reference
Ref 13J Med Chem. 2010 Jun 24;53(12):4731-48.Synthesis and characterization of in vitro and in vivo profiles of hydroxybupropion analogues: aids to smoking cessation. To Reference
Ref 14Bioorg Med Chem Lett. 2006 Aug 15;16(16):4283-6. Epub 2006 Jun 9.Aryloxyethylamines: binding at alpha7 nicotinic acetylcholine receptors. To Reference
Ref 15J Med Chem. 2010 Sep 9;53(17):6386-97.Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 receptor agonist with unprecedented selectivity and procognitive potential. To Reference
Ref 16J Med Chem. 2007 Dec 13;50(25):6383-91. Epub 2007 Nov 10.Synthesis and nicotinic acetylcholine receptor binding properties of bridged and fused ring analogues of epibatidine. To Reference
Ref 17Bioorg Med Chem. 2007 May 15;15(10):3368-72. Epub 2007 Mar 13.Aporphine metho salts as neuronal nicotinic acetylcholine receptor blockers. To Reference
Ref 18Bioorg Med Chem Lett. 2006 Nov 1;16(21):5493-7. Epub 2006 Aug 28.Epibatidine isomers and analogues: structure-activity relationships. To Reference
Ref 19Bioorg Med Chem Lett. 2006 Apr 1;16(7):2013-6. Epub 2006 Jan 18.Synthesis and analgesic activity of secondary amine analogues of pyridylmethylamine and positional isomeric analogues of ABT-594. To Reference
Ref 20Whiting PJ: The GABAA receptor gene family: new opportunities for drug development. Curr Opin Drug Discov Devel. 2003 Sep;6(5):648-57. To Reference


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