OPC-21268, an Orally Effective, Nonpeptide Vasopressin V1 Receptor Antagonist

Abstract

An orally effective, nonpeptide, vasopressin V1 receptor antagonist, OPC-21268, has been identified. This compound selectively antagonized binding to the V1 subtype of the vasopressin receptor in a competitive manner. In vivo, the compound acted as a specific antagonist of arginine vasopressin (AVP)-induced vasoconstriction. After oral administration in conscious rats, the compound also antagonized pressor responses to AVP. OPC-21268 can be used to study the physiological role of AVP and may be therapeutically useful in the treatment of hypertension and congestive heart failure.

Hyponatremia in cirrhosis: From pathogenesis to treatment

“…123 This compound was obtained as a result of structural changes in a selective nonpeptide V 1 antagonist. 157 Most existing information refers to this compound, but other nonpeptide, orally active, V 2 receptor antagonists have been described recently, including SR-121463A and VPA-985. [158][159][160] The potency and receptor selectivity of OPC-31260 was evaluated in in vitro receptor binding assays using rat liver plasma membranes for V 1 receptors and kidney plasma membranes for V 2 receptors.…”

Wortmannin inhibits the activation of MAP kinase following vasopressin V1 receptor stimulation

“…2A). The ICs~ of OPC-21268 for the displacement of specific AVP binding is reported to be 4x 10 -~ M and >10 -~ M for VI and V2 receptors, respectively [18], and the 1C~, of OPC-31260 for the displacement of specific AVP binding is reported to be 1.2 x 10 ~' M and 1.4 x 10 s M for VI and V2 receptors, respectively [19]. Thus.…”

Blocking Effects of OPC-21268 and OPC-31260 (Vasopressin V1- and V2-Receptor Antagonists) on Vasopressin-Induced Constrictions in Isolated, Perfused Dog Femoral Arteries

“…OPC-21268 selectively antagonized binding to the V1-subtype of the VP-receptor in a com petitive manner (4). In experiments in vivo, it acted as a specific antagonist of the VP-induced pressor re sponse in pithed rats and conscious rats (4).…”

“…Recently, nonpeptide V1 and V2-receptor antago nists were developed, i.e., OPC-21268 and OPC-31260, respectively (4,5). OPC-21268 selectively antagonized binding to the V1-subtype of the VP-receptor in a com petitive manner (4).…”