A specific antagonist of vasopressin produced plasma hyperosmolality and reduced ischemic-induced cerebral edema in rats.
Water diuresis was produced in rats after s.c. injections of d(CH2)5,D-Ile2,Ile4-AVP (compound 1) and d(CH2)5,Tyr(OEt)2Val4-AVP (compound 2). Compound 1 is known to be a more potent antagonist against the antidiuretic effect, while Compound 2 is a more potent antagonist against the vasopressor effect of vasopressin. Compound 1 (but not compound 2) also increased plasma osmolality significantly at the diuretic doses. In rats rendered ischemic of the forebrain by 4-hour occlusion of both common carotid arteries, the resulting increases in brain water were significantly reversed by the injection of compound 1. Compound 2 did not reduce the edema. The results suggests a novel approach to the treatment of cerebral edema.
Tang
A H
AH
CNS Diseases Research, Upjohn Company, Kalamazoo, MI 49001.
Ho
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PM
D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology; D001769:Blood / Q000187:drug effects; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D014667:Vasopressins / Q000037:antagonists & inhibitors*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
C056685:argipressin, beta-mercapto(beta,beta)-cyclopentamethylenepropionic acid(1)-Ile(2,4)-; D014667:Vasopressins; D001127:Arginine Vasopressin; C028884:1-(beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-2-(O-ethyl-Tyr)-4-Val-arginine vasopressin