YM218

YM218 is a novel, potent, nonpeptide vasopressin V1A receptor-selective antagonist with high selectivity over V1B, V2, and oxytocin receptors. It exhibits a Ki value of 0.30-0.50 nM for V1A receptors, demonstrating much lower affinity for V1B (1,510-25,500 nM), V2 (62.2-381 nM), and oxytocin receptors (71.0-150 nM). YM218 potently inhibits vasopressin-induced physiological responses including pressor responses, mesangial cell proliferation and hypertrophy, extracellular matrix production, and intracellular calcium increases. The compound displays a long duration of action (>8 hours at 3 mg/kg oral dose) and does not increase urine excretion, consistent with its V1A selectivity. YM218 was developed by Yamanouchi Pharmaceutical Co., Ltd. (later Astellas Pharma Inc.) as a pharmacological tool to investigate the physiological and pathophysiological roles of vasopressin in various conditions, particularly renal diseases.