Ispronicline

Ispronicline

Systematic (IUPAC) name
(2S,4E)-5-(5-isopropoxypyridin-3-yl)-N-methylpent-4-en-2-amine
Identifiers
CAS Number	252870-53-4
ATC code	none
PubChem	CID 9824145
ChemSpider	7999892
UNII	3E05NBH9V5
KEGG	D08935
Chemical data
Formula	C14H22N2O
Molar mass	234.336
SMILES C[C@@H](C/C=C/C1=CC(=CN=C1)OC(C)C)NC
InChI InChI=1S/C14H22N2O/c1-11(2)17-14-8-13(9-16-10-14)7-5-6-12(3)15-4/h5,7-12,15H,6H2,1-4H3/b7-5+/t12-/m0/s1 Key:RPCVIAXDAUMJJP-PZBABLGHSA-N
(what is this?)  (verify)

Ispronicline (TC-1734, AZD-3480) is an experimental drug which acts as a partial agonist at neural nicotinic acetylcholine receptors. It progressed to phase II clinical trials for the treatment of dementia and Alzheimer's disease, but is no longer under development.^[1]

Ispronicline is subtype-selective, binding primarily to the α4β2 subtype. It has antidepressant, nootropic and neuroprotective effects.

Early stage clinical trials showed that ispronicline was well tolerated, with the main side effects being dizziness and headache.^{[2][3][4][5][6]} However, mid stage clinical trials failed to show sufficient efficacy to continue development as a pharmaceutical drug.^[1]

References

1. Targacept Drops Development of Alzheimer's Drug
2. Gatto GJ, Bohme GA, Caldwell WS, Letchworth SR, Traina VM, Obinu MC, Laville M, Reibaud M, Pradier L, Dunbar G, Bencherif M. TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects. CNS Drug Reviews. 2004 Summer;10(2):147-66. PMID 15179444
3. Dunbar G, Demazières A, Monreal A, Cisterni C, Metzger D, Kuchibhatla R, Luthringer R. Pharmacokinetics and safety profile of ispronicline (TC-1734), a new brain nicotinic receptor partial agonist, in young healthy male volunteers. Journal of Clinical Pharmacology. 2006 Jul;46(7):715-26. PMID 16809797
4. Lippiello P, Letchworth SR, Gatto GJ, Traina VM, Bencherif M. Ispronicline: a novel alpha4beta2 nicotinic acetylcholine receptor-selective agonist with cognition-enhancing and neuroprotective properties. Journal of Molecular Neuroscience. 2006;30(1-2):19-20. PMID 17192610
5. Dunbar G, Boeijinga PH, Demazières A, Cisterni C, Kuchibhatla R, Wesnes K, Luthringer R. Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers. Psychopharmacology (Berlin). 2007 May;191(4):919-29. doi:10.1007/s00213-006-0675-x PMID 17225162
6. Dunbar GC, Inglis F, Kuchibhatla R, Sharma T, Tomlinson M, Wamsley J. Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI). Journal of Psychopharmacology. 2007 Mar;21(2):171-8. PMID 17329297