SB-334867 (SB 334867A) is a potent, selective, and blood-brain barrier permeable antagonist of the orexin-1 (OX1) receptor, demonstrating significant selectivity against OX2 (pKb=7.4), and exhibiting 100-fold selectivity over 5-HT2B and 5-HT2C, with pKi values of 5.4 and 5.3, respectively [1]. This compound effectively reduces ethanol consumption and obstructs the development of morphine-induced sensitization to locomotor activity in vivo [2] [3].

SB-334867 (100 pM– 10 μM) inhibits the orexin-A (10 nM) and orexin-B (100 nM)-induced calcium responses in a concentration-dependent manner, with apparent pK b values of 7.27±0.04 and 7.23±0.03. SB-334867 has no effect on the calcium response elicited by UTP (3 μM), which activates an endogenous purinergic receptor in CHO-OX1 and CHO-OX2 cells [4].

SB-334867 (intraperitoneal injection; 20 mg/kg; 20 days) administers 15 min before morphine injection can significantly reduce the effect of the morphine challenge dose in mice in comparison with the sporadically morphine-treated group [2].SB334867 (intraperitoneal injection; 3, 10 and 30 mg/kg) significantly reduces ethanol intake relative to vehicle and does not effect water consumption in female P rats [3].SB334867 (intraperitoneal injection; 3, 10 and 30 mg/kg) reduces ethanol consumption at the 30 mg/kg dose, high dose suppresses sucrose intake relative to vehicle, and it results in lower blood ethanol concentrations (BECs) relative to both the 10 and 30 mg/kg doses [3]. Animal Model: Male Swiss mice [2] Dosage: 20 mg/kg Administration: Intraperitoneal injection Result: Inhibited the acquisition of morphine-induced sensitization to locomotor activity of mice. Animal Model: C57BL/6J Mice [3] Dosage: 3, 10 and 30 mg/kg Administration: Intraperitoneal injection Result: Reduced ethanol consumption, BECs and suppressed sucrose intake in mice.