The Basic and Clinical Pharmacology of Nonpeptide Vasopressin Receptor Antagonists

DOI Web Site 被引用文献8件
  • M Thibonnier
    Departments of Medicine and Biochemistry, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106–4951;
  • P Coles
    Departments of Medicine and Biochemistry, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106–4951;
  • A Thibonnier
    Departments of Medicine and Biochemistry, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106–4951;
  • M Shoham
    Departments of Medicine and Biochemistry, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, Ohio 44106–4951;

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<jats:p> The neurohypophysial hormone arginine vasopressin (AVP) is a cyclic nonpeptide whose actions are mediated by the stimulation of specific G protein–coupled membrane receptors pharmacologically classified into V<jats:sub>1</jats:sub>-vascular (V<jats:sub>1</jats:sub>R), V<jats:sub>2</jats:sub>-renal (V<jats:sub>2</jats:sub>R) and V<jats:sub>3</jats:sub>-pituitary (V<jats:sub>3</jats:sub>R) AVP receptor subtypes. The random screening of chemical compounds and optimization of lead compounds recently resulted in the development of orally active nonpeptide AVP receptor antagonists. Potential therapeutic uses of AVP receptor antagonists include (a) the blockade of V<jats:sub>1</jats:sub>-vascular AVP receptors in arterial hypertension, congestive heart failure, and peripheral vascular disease; (b) the blockade of V<jats:sub>2</jats:sub>-renal AVP receptors in the syndrome of inappropriate vasopressin secretion, congestive heart failure, liver cirrhosis, nephrotic syndrome and any state of excessive retention of free water and subsequent dilutional hyponatremia; (c) the blockade of V<jats:sub>3</jats:sub>-pituitary AVP receptors in adrenocorticotropin-secreting tumors. The pharmacological and clinical profile of orally active nonpeptide vasopressin receptor antagonists is reviewed here. </jats:p>

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