Chemistry:Fipamezole
Fipamezole (INN; 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.[1][2][3][4][5] It is taken orally.[2][4]
The drug is a potent antagonist of the α2A-, α2B-, and α2C-adrenergic receptors (Ki = 9.2 nM, 17 nM, and 55 nM, respectively).[1][5] It also shows lower affinity for the histamine H1 and H3 receptors and for the serotonin transporter (SERT) (IC50 = 100–1,000 nM).[5] The drug reduces levodopa-induced dyskinesia and enhances levodopa's antiparkinsonian effects in rodents and monkeys.[1][5][6] 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.[7]
The chemical synthesis of fipamezole has been described.[1] It is made by the Balz-Schiemann reaction on Atipamezole.[8]
Fipamezole was first described in the scientific literature by 1999.[9] It was under development by Juvantia Pharma and Santhera Pharmaceuticals.[2][3] The drug reached phase 2 clinical trials prior to the discontinuation of its development.[2][3][4][1] Fipamezole missed its primary efficacy endpoint in the FJORD phase 2b trial published in 2012.[10][7]
See also
- List of investigational Parkinson's disease drugs
References
- ↑ 1.0 1.1 1.2 1.3 1.4 "Fipamezole Hydrochloride". Drugs of the Future 28 (1): 0014. 2003. doi:10.1358/dof.2003.028.01.716125. http://access.portico.org/stable?au=pjbf78xmn8s. Retrieved 1 February 2026.
- ↑ 2.0 2.1 2.2 2.3 "Fipamezole". 5 November 2023. https://adisinsight.springer.com/drugs/800012904.
- ↑ 3.0 3.1 3.2 "Delving into the Latest Updates on Fipamezole Hydrochloride with Synapse". 31 January 2026. https://synapse.patsnap.com/drug/7fe1145f7ed7466a8a0e637272733bc7.
- ↑ 4.0 4.1 4.2 "Fipamezole Drug Profile". 1 January 1900. https://pryzm.ozmosi.com/product/4750.
- ↑ 5.0 5.1 5.2 5.3 "Fipamezole (JP-1730) is a potent alpha2 adrenergic receptor antagonist that reduces levodopa-induced dyskinesia in the MPTP-lesioned primate model of Parkinson's disease". Movement Disorders 18 (8): 872–883. August 2003. doi:10.1002/mds.10464. PMID 12889076.
- ↑ "The α₂ adrenergic antagonist fipamezole improves quality of levodopa action in Parkinsonian primates". Movement Disorders 25 (13): 2084–2093. October 2010. doi:10.1002/mds.23172. PMID 20824735.
- ↑ 7.0 7.1 "Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study)". Neurology 79 (2): 163–169. July 2012. doi:10.1212/WNL.0b013e31825f0451. PMID 22744665.
- ↑ Karjalainen AJ, Virtanen RE, Karjalainen AL, Eloranta MM, Salonen JS, Sipilä HT, Haapalinna AS, "Substituted imidazole derivatives and their preparation and use", WO patent 1993/013074, published 8 July 1993
- ↑ "JP 1730, a novel alpha2-adrenoceptor antagonist, enhances apomorphine-and l-dopa-induced circling behavior in the rat.". Abstracts - Society for Neuroscience 25: 1344. 1999. https://scholar.google.com/scholar?cluster=17289959293667909154.
- ↑ "Non-dopaminergic treatments for motor control in Parkinson's disease". Drugs 73 (13): 1405–1415. September 2013. doi:10.1007/s40265-013-0105-4. PMID 23917951.
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