The basic and clinical pharmacology of nonpeptide vasopressin receptor antagonists

The neurohypophysial hormone arginine vasopressin (AVP) is a cyclic nonpept ide whose actions are mediated by the stimulation of specific G protein-cou pled membrane receptors pharmacologically classified into V-1-vascular (V1R ). V-2-renal (V2R) and V-3-pituitary (V3R) AVP receptor subtypes. The rando m screening of chemical compounds and optimization of lead compounds recent ly resulted in the development of orally active nonpeptide AVP receptor ant agonists. Potential therapeutic uses of AVP receptor antagonists include (a ) the blockade of V-1-vascular AVP receptors in arterial hypertension, cong estive heart failure, and peripheral vascular disease; (b) the blockade of V-2-renal AVP receptors in the syndrome of inappropriate vasopressin secret ion, congestive heart failure, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent dilutional hypona tremia; (c) the blockade of V-3-pituitary AVP receptors in adrenocorticotro pin-secreting tumors. The pharmacological and clinical profile of orally ac tive nonpeptide vasopressin receptor antagonists is reviewed here.