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

• Published in: Science (American Association for the Advancement of Science) Vol. 252; no. 5005; pp. 572 - 574
• Main Authors: Yamamura, Yoshitaka, Ogawa, Hidenori, Chihara, Tomihiko, Kondo, Kazumi, Onogawa, Toshiyuki, Nakamura, Shigeki, Mori, Toyoki, Tominaga, Michiaki, Yabuuchi, Youichi
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 26.04.1991; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Administration, Oral; Angiotensin II - pharmacology; Animals; Antibodies; Arginine Vasopressin - antagonists & inhibitors; Arginine Vasopressin - metabolism; Arginine Vasopressin - pharmacology; Binding, Competitive; Biochemistry; Biological and medical sciences; Blood pressure; Blood Pressure - drug effects; Cell Membrane - metabolism; Cell membranes; Dosage; Dose response relationship; Drugs; Heart; Hormones. Endocrine system; Kidney - metabolism; Kidneys; Kinetics; Liver; Liver - metabolism; Medical sciences; Norepinephrine - pharmacology; P branes; Pharmacology. Drug treatments; Piperidines - administration & dosage; Piperidines - pharmacology; Quinolones - administration & dosage; Quinolones - pharmacology; Rats; Receptors; Receptors, Angiotensin - drug effects; Receptors, Angiotensin - metabolism; Receptors, Vasopressin; Spectral bands; Therapy; Time Factors; Vasoconstrictor agents; Vasoconstrictors; Vasopressin; Vasopressins; Vertebrata; Mammalia; Rat; 8-Arginine vasopressin; Animal; Rodentia; Vasoconstriction; Oral administration; Antagonist; Biological receptor
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1850553

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.