Description
Istradefylline is a competitive inhibitor of adenosine A2A receptors that exhibits tremorlytic activity. Istradefylline is currently under examination as a potential treatment for Parkinson’s disease, as it decreases “off” time in subjects with Parkinson’s disease without worsening dyskinesia. Istradefylline increases dopamine levels in normal and 6-OHDA-lesioned animal models, improving cognitive performance. In other animal models, istradefylline decreases GABA release and elicits conditioned place preference (CPP) and increases locomotor activity, indicating a potential role for adenosine receptors in reward and reinforcement.
References
Kadowaki Horita T, Kobayashi M, Mori A, et al. Effects of the adenosine A2A antagonist istradefylline on cognitive performance in rats with a 6-OHDA lesion in prefrontal cortex. Psychopharmacology (Berl). 2013 Dec;230(3):345-52. PMID: 23748382.
Saki M, Yamada K, Koshimura E, et al. In vitro pharmacological profile of the A2A receptor antagonist istradefylline. Naunyn Schmiedebergs Arch Pharmacol. 2013 Nov;386(11):963-72. PMID: 23812646.
Mizuno Y, Hasegawa K, Kondo T, et al. Clinical efficacy of istradefylline (KW-6002) in Parkinson's disease: a randomized, controlled study. Mov Disord. 2010 Jul 30;25(10):1437-43. PMID: 20629136.
Salamone JD, Betz AJ, Ishiwari K, et al. Tremorolytic effects of adenosine A2A antagonists: implications for parkinsonism. Front Biosci. 2008 May 1;13:3594-605. PMID: 18508458.
Harper LK, Beckett SR, Marsden CA, et al. Effects of the A 2A adenosine receptor antagonist KW6002 in the nucleus accumbens in vitro and in vivo. Pharmacol Biochem Behav. 2006 Jan;83(1):114-21. PMID: 16451807.
