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  • 标题:A Novel Vasopressin Dual V1A/V2 Receptor Antagonist, Conivaptan Hydrochloride, Improves Hyponatremia in Rats with Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)
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  • 作者:Koh-ichi Wada ; Utane Matsukawa ; Akira Fujimori
  • 期刊名称:Biological and Pharmaceutical Bulletin
  • 印刷版ISSN:0918-6158
  • 电子版ISSN:1347-5215
  • 出版年度:2007
  • 卷号:30
  • 期号:1
  • 页码:91-95
  • DOI:10.1248/bpb.30.91
  • 出版社:The Pharmaceutical Society of Japan
  • 摘要:We investigated the effects of intravenous administration of conivaptan hydrochloride, a dual vasopressin V1A and V2 receptor antagonist, on blood electrolytes and plasma osmolality in rats with an experimental syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The experimental SIADH rat model was developed by means of continuous administration of arginine vasopressin (AVP) via a subcutaneously implanted osmotic mini pump, and hyponatremia was induced by additional water loading. This model possesses similar characteristics to those observed in patients with SIADH, specifically decreases in blood sodium concentration and plasma osmolality. In this experimental model, intravenous administration of conivaptan (0.1, 1 mg/kg) significantly increased blood sodium concentration and plasma osmolality. On the other hand, intravenous administration of furosemide (10 mg/kg) did not increase either blood sodium concentration or plasma osmolality in the SIADH rats. Moreover, furosemide significantly lowered blood potassium concentration. These results show that conivaptan improves hyponatremia in rats with SIADH, supporting the therapeutic potential of conivaptan in treatment of patients with hyponatremia associated with SIADH.
  • 关键词:conivaptan;SIADH;hyponatremia;vasopressin V2 receptor;aquaretic effect;furosemide
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