SB-334867

SB-334867 has excellent selectivity for the orexin-1 receptor, blood-brain barrier permeability and shows in vivo activity following ip dosing. SB-334867-A is a non-peptide OX(1) selective receptor antagonist. PKb values are 7.2 and < 5 for inhibition of intracellular Ca2+ release in CHO cells expressing human OX1 and OX2 receptors respectively. SB-334867 blocks orexin-A induced grooming and feeding following systemic administration in vivo. SB-334867-A (OX1, pKB = 7.4; OX2, pKB = 5.7), devoid of appreciable affinity for either 5-HT2B (pKi < 5.3) or 5-HT2C (pKi < 5.4) receptors, provides the first definitive evidence that a central behavioural effect of orexin-A (grooming) is mediated by OX1 receptors.