Ispronicline

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

Clinical data
ATC code	none
Identifiers
IUPAC name (2S,4E)-5-(5-isopropoxypyridin-3-yl)-N-methylpent-4-en-2-amine
CAS Number	252870-53-4^Y
PubChem CID	9824145
ChemSpider	7999892^N
UNII	3E05NBH9V5
KEGG	D08935^Y
Chemical and physical data
Formula	C14H22N2O
Molar mass	234.336 g·mol^−1
3D model (JSmol)	Interactive image
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^N Key:RPCVIAXDAUMJJP-PZBABLGHSA-N^N
^NY (what is this?)  (verify)

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, et al. (2004). "TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects". CNS Drug Reviews. 10 (2): 147–66. doi:10.1111/j.1527-3458.2004.tb00010.x. PMC 6741718. PMID 15179444.
3. Dunbar G, Demazières A, Monreal A, Cisterni C, Metzger D, Kuchibhatla R, Luthringer R (July 2006). "Pharmacokinetics and safety profile of ispronicline (TC-1734), a new brain nicotinic receptor partial agonist, in young healthy male volunteers". Journal of Clinical Pharmacology. 46 (7): 715–26. doi:10.1177/0091270006288730. PMID 16809797.
4. Lippiello P, Letchworth SR, Gatto GJ, Traina VM, Bencherif M (2006). "Ispronicline: a novel alpha4beta2 nicotinic acetylcholine receptor-selective agonist with cognition-enhancing and neuroprotective properties". Journal of Molecular Neuroscience. 30 (1–2): 19–20. doi:10.1385/JMN:30:1:19. PMID 17192610.
5. Dunbar G, Boeijinga PH, Demazières A, Cisterni C, Kuchibhatla R, Wesnes K, Luthringer R (May 2007). "Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers". Psychopharmacology. 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 (March 2007). "Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI)". Journal of Psychopharmacology. 21 (2): 171–8. doi:10.1177/0269881107066855. PMID 17329297.