We have evaluated the efficacy of @entity46463 , a new orally active and specific vasopressin V1 receptor antagonist ( @entity369 -vasopressin [ @entity1831 ]), in the blockade of the vascular effects of exogenous @entity1831 in healthy subjects. In preliminary experiments, two procedures to measure the V1 vascular effects of @entity1831 were assessed. First, the @entity1831 -induced changes in skin blood flow were investigated by the injection of increasing doses of @entity1831 intradermally, with or without a previous local vasodilation with @entity10132 ( @entity10132 ). In a second protocol, @entity1831 was infused intra-arterially, and the changes in radial artery diameter and blood flow were measured. The intradermal injection of @entity1831 caused significant decreases in skin blood flow, and the use of @entity10132 increased the sensitivity of the method by a factor of 10(2) to 10(3). @entity1831 infused intra-arterially caused dose-dependent decreases in the radial artery diameter and blood flow. In the main study, the potency and efficacy of @entity46463 to block the @entity1831 -induced changes in skin blood flow were assessed in 12 healthy @entity1 with a double-blind, triple crossover study design. The subjects were randomized to receive a placebo orally and 30 mg and 300 mg of the antagonist at a 1-week interval. The subjects were then further randomized to evaluate the efficacy of the same doses of the antagonist to block the vasoconstriction of the radial artery induced by an intra-arterial infusion of @entity1831 . @entity46463 inhibits, dose-dependently and significantly, the @entity1831 -induced changes in skin blood flow, with a peak effect occurring between 2 and 6 hours after injection. In addition, the 300-mg dose of @entity46463 completely blocked the vasoconstriction of the radial artery induced by @entity1831 . In conclusion, skin blood-flow measurement, after intradermal injection of @entity1831 on a skin area vasodilated with @entity10132 , is an effective method to investigate the V1 vascular effect of @entity1831 in @entity1 . @entity46463 is a potent and specific antagonist of V1 receptors, which blocks the @entity1831 -induced vasoconstriction.

Effects of @entity46463 , a new orally active and specific vasopressin V1 receptor antagonist, on vasopressin-induced vasoconstriction in XXXX .

@entity1831 :: ('CHEBI:34543', 'Chemical') :: ['AVP'] @entity1 :: ('9606', 'Species') :: ['men', 'humans'] @entity10132 :: ('796', 'Gene') :: ['CGRP', 'calcitonin gene-related peptide'] @entity46463 :: ('MESH:C082134', 'Chemical') :: ['SR 49059'] @entity369 :: ('CHEBI:29016', 'Chemical') :: ['arginine']
@entity1 :: (9606,Species) :: ['humans']
