Ispronicline Explained

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]

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^{[2] [3]}

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.^{[4] [5] [6] [7] [8]} However, mid-stage clinical trials failed to show sufficient efficacy to continue development as a pharmaceutical drug.^[1]

See also

• Rivanicline

Notes and References

1. Web site: Armental M . 14 July 2014 . Wall Street Journal . Targacept Drops Development of Alzheimer's Drug .
2. Potter AS, Dunbar G, Mazzulla E, Hosford D, Newhouse PA . AZD3480, a novel nicotinic receptor agonist, for the treatment of attention-deficit/hyperactivity disorder in adults . Biological Psychiatry . 75 . 3 . 207–214 . February 2014 . 23856296 . 10.1016/j.biopsych.2013.06.002 . 44717647 .
3. Web site: AstraZeneca. 2009-10-29. Targacept Inc.. An Exploratory Trial of AZD3480 (TC-1734) for the Treatment of Adult Attention-Deficit/Hyperactivity Disorder (ADHD).
4. 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 . 10 . 2 . 147–166 . 2004 . 15179444 . 6741718 . 10.1111/j.1527-3458.2004.tb00010.x .
5. 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 . 46 . 7 . 715–726 . July 2006 . 16809797 . 10.1177/0091270006288730 . 22499622 .
6. 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 . 30 . 1–2 . 19–20 . 2006 . 17192610 . 10.1385/JMN:30:1:19 . 195688187 .
7. 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 . 191 . 4 . 919–929 . May 2007 . 17225162 . 10.1007/s00213-006-0675-x . 10920515 .
8. 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 . 21 . 2 . 171–178 . March 2007 . 17329297 . 10.1177/0269881107066855 . 10056476 .