Surprising pharmacological activity of analogues 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 arginine 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 activities 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 vasopressor response to AVP. Moreover, it is the first V-1-antagonist devoid of anti-uterotonic activity. High antipressor potency of the second peptide was achieved without modification of position 1.