OPC 21268 is a nonpeptide antagonist of vasopressin V1 receptors (IC50 = 0.4 μM in rat liver membranes). It is selective for V1 over V2 receptors (IC50 = >100 μM in kidney membranes). It is also selective for rat over human V1 receptors (Kis = 25 and 8,800 nM, respectively), which can be partially attributed to the alanine residue at position 337 of the rat sequence, instead of a glycine residue in the human sequence, with differences at positions 224, 310, and 324 also contributing. OPC 21268 (0.03-1 mg/kg, i.v.) inhibits pressor responses induced by arginine vasopressin (argipressin; ) in pithed rats and arginine vasopressin-induced vasoconstriction in conscious rats (ID50 = 2 mg/kg). It induces hypotension in aged spontaneously hypertensive rats (SHRs) and stroke-prone SHRs when administered at a dose of 3 mg/kg.
