OPC 21268

OPC 21268 is a nonpeptide antagonist of vasopressin V₁ receptors (IC₅₀ = 0.4 µM in rat liver membranes).¹ It is selective for V₁ over V₂ receptors (IC₅₀ = >100 µM in kidney membranes). It is also selective for rat over human V₁ receptors (K_is = 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; Item No. 24154) in pithed rats and arginine vasopressin-induced vasoconstriction in conscious rats (ID₅₀ = 2 mg/kg).² It induces hypotension in aged spontaneously hypertensive rats (SHRs) and stroke-prone SHRs when administered at a dose of 3 mg/kg.³

WARNING This product is not for human or veterinary use.

1. Thibonnier, M., Coles, P., Conarty, D.M., et al. A molecular model of agonist and nonpeptide antagonist binding to the human V1 vascular vasopressin receptor. J. Pharmacol. Exp. Ther. 4(1), 195-203 (2000).

2. Yamamura, Y., Ogawa, H., Chihara, T., et al. OPC-21268, an orally effective, nonpeptide vasopressin V1 receptor antagonist. Science 252(5005), 572-574 (1991).

3. Yamada, Y., Yamamura, Y., Chihara, T., et al. OPC-21268, a vasopressin V1 antagonist, produces hypotension in spontaneously hypertensive rats. Hypertension 23(2), 200-204 (1994).