0054 SUVN-G3031, a Histamine H3 Receptor Inverse Agonist Produces Wake Promoting Effect in Orexin-2-saporin Lesioned Rats

[摘要] IntroductionSUVN-G3031, a potent histamine H3 receptor inverse agonist is being developed for the treatment of narcolepsy and other sleep related disorders. SUVN-G3031 has hKi of 8.7 nM at H3R with more than 100-fold selectivity against related GPCRs. SUVN-G3031 exhibited desired pharmacokinetic properties and brain penetration in preclinical species. SUVN-G3031 blocked R-α-methylhistamine induced water intake and increased tele-methylhistamine levels in brain and cerebrospinal fluid. Acute oral administration of SUVN-G3031 produced significant increase in acetylcholine, histamine, dopamine and norepinephrine levels in the cortex. SUVN-G3031 produced wake promoting effects in male Wistar rats and C57BL/6J mice. SUVN-G3031 was evaluated in Phase 1 clinical studies (US IND). It showed desirable pharmacokinetic profile with safety and tolerability in healthy human volunteers.

[学科分类] 生理学