pitolisant   Click here for help

GtoPdb Ligand ID: 8924

Synonyms: BF2.649 | Ozawade® | tiprolisant [USAN] | Wakix®
Approved drug
pitolisant is an approved drug (EMA (2016), FDA (2019))
Compound class: Synthetic organic
Comment: Pitolisant is a selective antagonist/inverse agonist of the histamine H3 receptor [7-8,11].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 8
Topological polar surface area 12.47
Molecular weight 295.17
XLogP 3.94
No. Lipinski's rules broken 0
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Canonical SMILES Clc1ccc(cc1)CCCOCCCN1CCCCC1
Isomeric SMILES Clc1ccc(cc1)CCCOCCCN1CCCCC1
InChI InChI=1S/C17H26ClNO/c18-17-9-7-16(8-10-17)6-4-14-20-15-5-13-19-11-2-1-3-12-19/h7-10H,1-6,11-15H2
1. Celanire S, Wijtmans M, Talaga P, Leurs R, de Esch IJ. (2005)
Keynote review: histamine H3 receptor antagonists reach out for the clinic.
Drug Discov Today, 10 (23-24): 1613-27. [PMID:16376822]
2. Kollb-Sielecka M, Demolis P, Emmerich J, Markey G, Salmonson T, Haas M. (2017)
The European Medicines Agency review of pitolisant for treatment of narcolepsy: summary of the scientific assessment by the Committee for Medicinal Products for Human Use.
Sleep Med, 33: 125-129. [PMID:28449891]
3. Ligneau X, Landais L, Perrin D, Piriou J, Uguen M, Denis E, Robert P, Parmentier R, Anaclet C, Lin JS et al.. (2007)
Brain histamine and schizophrenia: potential therapeutic applications of H3-receptor inverse agonists studied with BF2.649.
Biochem Pharmacol, 73 (8): 1215-24. [PMID:17343831]
4. Ligneau X, Perrin D, Landais L, Camelin JC, Calmels TP, Berrebi-Bertrand I, Lecomte JM, Parmentier R, Anaclet C, Lin JS et al.. (2007)
BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.
J Pharmacol Exp Ther, 320 (1): 365-75. [PMID:17005916]
5. Lin JS, Dauvilliers Y, Arnulf I, Bastuji H, Anaclet C, Parmentier R, Kocher L, Yanagisawa M, Lehert P, Ligneau X et al.. (2008)
An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients.
Neurobiol Dis, 30 (1): 74-83. [PMID:18295497]
6. Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WL, Stark H, Thurmond RL, Haas HL. (2015)
International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.
Pharmacol Rev, 67 (3): 601-55. [PMID:26084539]
7. Pierson PD, Fettes A, Freichel C, Gatti-McArthur S, Hertel C, Huwyler J, Mohr P, Nakagawa T, Nettekoven M, Plancher JM et al.. (2009)
5-hydroxyindole-2-carboxylic acid amides: novel histamine-3 receptor inverse agonists for the treatment of obesity.
J Med Chem, 52 (13): 3855-68. [PMID:19456097]
8. Schwartz JC. (2011)
The histamine H3 receptor: from discovery to clinical trials with pitolisant.
Br J Pharmacol, 163 (4): 713-21. [PMID:21615387]
9. Stocking EM, Letavic MA. (2008)
Histamine H3 antagonists as wake-promoting and pro-cognitive agents.
Curr Top Med Chem, 8 (11): 988-1002. [PMID:18673168]
10. Szakacs Z, Dauvilliers Y, Mikhaylov V, Poverennova I, Krylov S, Jankovic S, Sonka K, Lehert P, Lecomte I, Lecomte JM et al.. (2017)
Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial.
Lancet Neurol, 16 (3): 200-207. [PMID:28129985]
11. Łazewska D, Kuder K, Ligneau X, Camelin JC, Schunack W, Stark H, Kieć-Kononowicz K. (2009)
Diether derivatives of homo- or substituted piperidines as non-imidazole histamine H3 receptor ligands.
Bioorg Med Chem, 17 (8): 3037-42. [PMID:19329325]