Fipamezole (; developmental code names BVF-025 and JP-1730) is an α2-adrenergic receptor antagonist which was under development for the treatment of Parkinson's disease but was never marketed. It is taken orally.
The drug is a potent antagonist of the α2A-, α2B-, and α2C-adrenergic receptors (Ki = 9.2nM, 17nM, and 55nM, respectively). It also shows lower affinity for the histamine H1 and H3 receptors and for the serotonin transporter (SERT) ( = 100–1,000nM). The drug reduces levodopa-induced dyskinesia and enhances levodopa's antiparkinsonian effects in rodents and monkeys. Side effects of fipamezole in humans occurring more often than with placebo included mild transiently increased blood pressure, nausea and vomiting, dysgeusia, oral hypoesthesia, and flushing.
The chemical synthesis of fipamezole has been described. It is made by the Balz-Schiemann reaction on Atipamezole.
Fipamezole was first described in the scientific literature by 1999. It was under development by Juvantia Pharma and Santhera Pharmaceuticals. The drug reached phase 2 clinical trials prior to the discontinuation of its development. Fipamezole missed its primary efficacy endpoint in the FJORD phase 2b trial published in 2012.
See also List of investigational Parkinson's disease drugs
References