Analogues of arginine vasopressin modified in position 2 or 3 with naphthylalanine: Selective antagonists of oxytocin in-vitro

In this study we describe the synthesis and some pharmacological properties of six new analogues of arginine vasopressin (AVP). Five of the peptides were substituted in position 2 with L-1-naphthylalanin e (L-1-Nal) or D-1-naphthylalanine (D-1-Nal); one had D-1-Nal in position 3 . All analogues were tested in bioassays for presser and antidiuretic activ ity. We also tested the uterotonic activity of the peptides in-vitro: Two o f the new peptides were moderately potent V-1a and oxytocin antagonists. Th e modifications proposed resulted in a drop or the removal of antidiuretic activity and in the removal of presser activity, or conversion into moderat e antagonists. Two peptides ([Mpa(1), (L-1-Nal)(2)]AVP and [Mpa(1), (D-1-Na l)(2)]AVP) which appear not to interact with V-1a and V-2 receptors were ex ceptionally selective oxytocin antagonists in-vitro. These compounds with selective oxytocin antagonistic activity may be promis ing candidates for the development of potential tocolytic agents for the pr evention of pre-term labour.