ispronicline

{{Short description|Chemical compound}}

{{cs1 config|name-list-style=vanc|display-authors=6}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 444274830

| IUPAC_name = (2S,4E)-5-(5-isopropoxypyridin-3-yl)-N-methylpent-4-en-2-amine

| image = Ispronicline Structure.svg

| width = 240

| tradename =

| routes_of_administration =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 252870-53-4

| ATC_prefix = none

| ATC_suffix =

| PubChem = 9824145

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 3E05NBH9V5

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D08935

| DrugBank =

| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}}

| ChemSpiderID = 7999892

| C=14 | H=22 | N=2 | O=1

| smiles = C[C@@H](C/C=C/C1=CC(=CN=C1)OC(C)C)NC

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = RPCVIAXDAUMJJP-PZBABLGHSA-N

}}

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.{{cite web | vauthors = Armental M | date = 14 July 2014 | work = Wall Street Journal | url = https://www.wsj.com/articles/targacept-drops-development-of-alzheimers-drug-1405367773 | title = Targacept Drops Development of Alzheimer's Drug }}

It has also progressed to phase II as a potential treatment for ADHD. With dosages of 50 mg/day showing a significant improvement in ADHD symptoms{{cite journal | vauthors = Potter AS, Dunbar G, Mazzulla E, Hosford D, Newhouse PA | title = AZD3480, a novel nicotinic receptor agonist, for the treatment of attention-deficit/hyperactivity disorder in adults | journal = Biological Psychiatry | volume = 75 | issue = 3 | pages = 207–214 | date = February 2014 | pmid = 23856296 | doi = 10.1016/j.biopsych.2013.06.002 | s2cid = 44717647 }}{{Cite web |last=AstraZeneca|date=2009-10-29|others=Targacept Inc.|title=An Exploratory Trial of AZD3480 (TC-1734) for the Treatment of Adult Attention-Deficit/Hyperactivity Disorder (ADHD)|url=https://clinicaltrials.gov/ct2/show/study/NCT00683462}}

Ispronicline is subtype-selective, binding primarily to the α4β2 subtype. It has antidepressant, nootropic and neuroprotective effects.{{medcn|date=July 2014}}

Early stage clinical trials showed that ispronicline was well tolerated, with the main side effects being dizziness and headache.{{cite journal | vauthors = Gatto GJ, Bohme GA, Caldwell WS, Letchworth SR, Traina VM, Obinu MC, Laville M, Reibaud M, Pradier L, Dunbar G, Bencherif M | title = TC-1734: an orally active neuronal nicotinic acetylcholine receptor modulator with antidepressant, neuroprotective and long-lasting cognitive effects | journal = CNS Drug Reviews | volume = 10 | issue = 2 | pages = 147–166 | year = 2004 | pmid = 15179444 | pmc = 6741718 | doi = 10.1111/j.1527-3458.2004.tb00010.x }}{{cite journal | vauthors = Dunbar G, Demazières A, Monreal A, Cisterni C, Metzger D, Kuchibhatla R, Luthringer R | title = Pharmacokinetics and safety profile of ispronicline (TC-1734), a new brain nicotinic receptor partial agonist, in young healthy male volunteers | journal = Journal of Clinical Pharmacology | volume = 46 | issue = 7 | pages = 715–726 | date = July 2006 | pmid = 16809797 | doi = 10.1177/0091270006288730 | s2cid = 22499622 }}{{cite journal | vauthors = Lippiello P, Letchworth SR, Gatto GJ, Traina VM, Bencherif M | title = Ispronicline: a novel alpha4beta2 nicotinic acetylcholine receptor-selective agonist with cognition-enhancing and neuroprotective properties | journal = Journal of Molecular Neuroscience | volume = 30 | issue = 1–2 | pages = 19–20 | year = 2006 | pmid = 17192610 | doi = 10.1385/JMN:30:1:19 | s2cid = 195688187 }}{{cite journal | vauthors = Dunbar G, Boeijinga PH, Demazières A, Cisterni C, Kuchibhatla R, Wesnes K, Luthringer R | title = Effects of TC-1734 (AZD3480), a selective neuronal nicotinic receptor agonist, on cognitive performance and the EEG of young healthy male volunteers | journal = Psychopharmacology | volume = 191 | issue = 4 | pages = 919–929 | date = May 2007 | pmid = 17225162 | doi = 10.1007/s00213-006-0675-x | s2cid = 10920515 }}{{cite journal | vauthors = Dunbar GC, Inglis F, Kuchibhatla R, Sharma T, Tomlinson M, Wamsley J | title = Effect of ispronicline, a neuronal nicotinic acetylcholine receptor partial agonist, in subjects with age associated memory impairment (AAMI) | journal = Journal of Psychopharmacology | volume = 21 | issue = 2 | pages = 171–178 | date = March 2007 | pmid = 17329297 | doi = 10.1177/0269881107066855 | s2cid = 10056476 }} However, mid-stage clinical trials failed to show sufficient efficacy to continue development as a pharmaceutical drug.