Surprising Pharmacological Activity of Analogues Designed by Substitution of Position 3 in Arginine Vasopressin (AVP) and 8-D-Arginine Vasopressin with l-2-Naphthylalanine

Abstract

Abstract In an attempt to develop more active and selective analogues of arginine vasopressin (AVP), two peptides have been designed, synthesized and tested for vasopressor (V1-receptors) and antidiuretic (V2-receptors) activities. We also estimated the uterotonic and anti-uterotonic activities of these compounds in-vitro. The first peptide, [(l-2-Nal)3] AVP is a highly active V2-agonist. The second analogue, [(l-2-Nal)3, (d-Arg)8]VP is among the most potent antagonists of the vasopressor response to AVP. Moreover, it is the first V1-antagonist devoid of anti-uterotonic activity. High antipressor potency of the second peptide was achieved without modification of position 1.