[1-(.beta.-Mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid),4-valine, 8-D-arginine]vasopressin, a potent and selective inhibitor of the vasopressor response to arginine-vasopressin

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Abstract
[1-(.beta.-Mercapto-.beta.,.beta.-cyclopentamethylenepropionic acid),4-valine,8-D-arginine]vasopressin [d(CH2)5VDAVP] was synthesized and assayed for antidiuretic, vasopressor and oxytocic activities in rats. The required protected intermediate was synthesized by a combination of solid-phase synthesis and an [8 + 1] coupling in solution. d(CH2)5VDAVP has an antidiuretic potency of 0.10 .+-. 0.02 unit/mg, less than 1/10,000 that of its parent [deamino,4-valine,8-D-arginine]vasopressin (dVDADP). d(CH2)SVDAVP is a specific antagonist of the vasopressor responses to AVP [arginine-vasopressin]. It has an antivasopressor pA2 value of 7.68 .+-. 0.05 when tested against AVP. It is also an antagonist of the in vitro oxytocic response to oxytocin (pA2 value = 6.62 .+-. 0.07). With its negligible antidiuretic activity, absence of oxytocic activity and its potent and specific ability to antagonize the vasopressor effects of AVP, d(CH2)5VDAVP is one of the most potent and selective vasopressor antagonists reported to date. It should be a useful tool with which to probe the possible role(s) that AVP may play in cardiovascular regulation under normal and pathological conditions.