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Fipamezole

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Fipamezole
Clinical data
Other namesBVF-025; BVF025; JP-1730; JP1730
Routes of
administration		Oral[1][2]
Drug classα2-Adrenergic receptor antagonist
ATC code
  • None
Pharmacokinetic data
Elimination half-life1.2–3.5 hours[3]
Identifiers
  • 5-(2-ethyl-5-fluoro-1,3-dihydroinden-2-yl)-1H-imidazole
CAS Number
PubChem CID
DrugBank
UNII
ChEMBL
Chemical and physical data
FormulaC14H15FN2
Molar mass230.286 g·mol−1
3D model (JSmol)
  • CCC1(CC2=C(C1)C=C(C=C2)F)C3=CN=CN3
  • InChI=1S/C14H15FN2/c1-2-14(13-8-16-9-17-13)6-10-3-4-12(15)5-11(10)7-14/h3-5,8-9H,2,6-7H2,1H3,(H,16,17)
  • Key:KXSUAWAUCNFBQJ-UHFFFAOYSA-N

Fipamezole (INNTooltip International Nonproprietary Name; 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.[3][1][4][2][5] It is taken orally.[1][2]

The drug is a potent antagonist of the α2A-, α2B-, and α2C-adrenergic receptors (Ki = 9.2 nM, 17 nM, and 55 nM, respectively).[3][5] It also shows lower affinity for the histamine H1 and H3 receptors and for the serotonin transporter (SERT) (IC50Tooltip half-maximal inhibitory concentration = 100–1,000 nM).[5] The drug reduces levodopa-induced dyskinesia and enhances levodopa's antiparkinsonian effects in rodents and monkeys.[3][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.[3] 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.[1][4] The drug reached phase 2 clinical trials prior to the discontinuation of its development.[1][4][2][3] Fipamezole missed its primary efficacy endpoint in the FJORD phase 2b trial published in 2012.[10][7]

See also

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References

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  1. ^ a b c d e "Fipamezole". AdisInsight. 5 November 2023. Retrieved 1 February 2026.
  2. ^ a b c d "Fipamezole Drug Profile". Ozmosi. 1 January 1900. Retrieved 1 February 2026.
  3. ^ a b c d e f Sorbera LA, Castaner J, Bayes M (2003). "Fipamezole Hydrochloride". Drugs of the Future. 28 (1): 0014. doi:10.1358/dof.2003.028.01.716125. Retrieved 1 February 2026.
  4. ^ a b c "Delving into the Latest Updates on Fipamezole Hydrochloride with Synapse". Synapse. 31 January 2026. Retrieved 1 February 2026.
  5. ^ a b c d Savola JM, Hill M, Engstrom M, Merivuori H, Wurster S, McGuire SG, et al. (August 2003). "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. doi:10.1002/mds.10464. PMID 12889076.
  6. ^ Johnston TH, Fox SH, Piggott MJ, Savola JM, Brotchie JM (October 2010). "The α₂ adrenergic antagonist fipamezole improves quality of levodopa action in Parkinsonian primates". Movement Disorders. 25 (13): 2084–2093. doi:10.1002/mds.23172. PMID 20824735.
  7. ^ a b Lewitt PA, Hauser RA, Lu M, Nicholas AP, Weiner W, Coppard N, et al. (July 2012). "Randomized clinical trial of fipamezole for dyskinesia in Parkinson disease (FJORD study)". Neurology. 79 (2): 163–169. doi:10.1212/WNL.0b013e31825f0451. PMID 22744665.
  8. ^ WO 1993/013074, Karjalainen AJ, Virtanen RE, Karjalainen AL, Eloranta MM, Salonen JS, Sipilä HT, Haapalinna AS, "Substituted imidazole derivatives and their preparation and use", published 8 July 1993, assigned to Orion Oyj 
  9. ^ Honkanen A, Ingman K, Korpi ER, Savola JM (1999). "JP 1730, a novel alpha2-adrenoceptor antagonist, enhances apomorphine-and l-dopa-induced circling behavior in the rat". Abstracts - Society for Neuroscience. 25: 1344.
  10. ^ Fox SH (September 2013). "Non-dopaminergic treatments for motor control in Parkinson's disease". Drugs. 73 (13): 1405–1415. doi:10.1007/s40265-013-0105-4. PMID 23917951.