SURPRISING PHARMACOLOGICAL ACTIVITY OF ANALOGS DESIGNED BY SUBSTITUTION OF POSITION-3 IN ARGININE-VASOPRESSIN (AVP) AND 8-D-ARGININE VASOPRESSIN WITH L-2-NAPHTHYLALANINE

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