Pitolisant oxalate

• CAT Number: I003333
• CAS Number: 362665-57-4
• Molecular Formula: C19H28ClNO5
• Molecular Weight: 385.88
• Purity: ≥95%
• Synonyms: 1-(3-(3-(4-chlorophenyl)propoxy)propyl)piperidine oxalate
• Target: Histamine Receptor
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 0.16 nM (Ki value); 1.5 nM (EC50) [1]

Pitolisant oxalate (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor (Ki=0.16 nM).IC50 Value: 0.16 nM (Ki value); 1.5 nM (EC50) [1]Target: H3 receptorBF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan.in vitro: BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Pitolisant in vitro potency was approximately 6 times lower at the rodent receptor [1].in vivo: In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days [1]. A statistically significant suppressive effect (standardized photosensitive response [SPR] reduction as measured with paired t-tests) for 20-, 40-, or 60-mg doses of pitolisant was seen in 9/14 (64%) patients of whom 6/14 (43%) showed abolition of the response to intermittent photic stimulation (IPS) [2]. BF2.649 showed significant inhibitory activity in several mouse models of schizophrenia [3].Clinical trial: HARMONYIII: Long-term, Open-label Study in Narcolepsy With BF2.649 (Pitolisant). Phase3

Reference

[1]. Ligneau X, Perrin D, Landais L, 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. 2007 Jan;320(1):365-75.
[2]. Kasteleijn-Nolst Trenité D, Parain D, Genton P, Efficacy of the histamine 3 receptor (H3R) antagonist pitolisant (formerly known as tiprolisant; BF2.649) in epilepsy: Dose-dependent effects in the human photosensitivity model. Epilepsy Behav. 2013 Jul;28(1):66-70.
[3]. Ligneau X, Landais L, Perrin D, Brain histamine and schizophrenia: potential therapeutic applications of H3-receptor inverse agonists studied with BF2.649. Biochem Pharmacol. 2007 Apr 15;73(8):1215-24.