GSK1059865

GSK1059865 is a potent orexin 1 receptor antagonist. IC50 & Target: Orexin 1 receptor^[1] In Vivo: Treatment with GSK1059865 significantly decreases ethanol drinking in a dose-dependent manner in CIE-exposed mice. In contrast GSK1059865 decreases drinking in air-exposed mice only at the highest dose used. There is no effect of GSK1059865 on sucrose intake^[1]. GSK1059865 (0.3 nM-10 nM) produces non-surmountable antagonism with a dose-dependent rightward shift of the OXA EC₅₀ and a concomitant decrease of the agonist maximal response. The calculated pK_B value is 8.77±0.12 for GSK1059865. GSK1059865 (0.1-3.3 μM) produces a classical surmountable profile with parallel rightward shift of the OXA EC₅₀ without depression of the agonist maximal response^[2]. Intraperitoneal administration of GSK1059865 produces a region-dependent inhibition of yohimbine-induced relative cerebral blood volume response. The administration of GSK1059865 per se produces a weak relative cerebral blood volume increase in several brain regions. GSK1059865-pretreated animals exhibit slightly higher baseline mean arterial blood pressure values than controls^[3].