A Novel Vasopressin Dual V_<1A>/V_2 Receptor Antagonist, Conivaptan Hydrochloride, Improves Hyponatremia in Rats with Syndrome of Inappropriate Secretion of Antidiuretic Hormone (SIADH)(Pharmacology)

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概要

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• We investigated the effects of intravenous administration of conivaptan hydrochloride, a dual vasopressin V_<1A> and V_2 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, 1mg/kg) significantly increased blood sodium concentration and plasma osmolality. On the other hand, intravenous administration of furosemide (10mg/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.

• 公益社団法人日本薬学会の論文
• 2007-01-01

著者

• ARAI Yukinori

  Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

• FUJIMORI Akira

  Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

• SASAMATA Masao

  Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

• MIYATA Keiji

  Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

• Miyata Keiji

  Applied Pharmacology Res. Laboratories Drug Discovery Res. Astellas Pharma Inc. Jpn

• Miyata Keiji

  Pharmacology Laboratories Institute For Drug Discovery Research Yamanouchi Pharmaceutical Co. Ltd.

• Arai Yukinori

  Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.

• Sasamata Masao

  Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.

• Sasamata Masao

  Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.

• Fujimori Akira

  Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.

• Sudoh Katsumi

  Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.

• Wada Koh-ichi

  Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.

• MATSUKAWA Utane

  Clinical Development Administration, Development, Astellas Pharma Inc.

• FUJIMORI Akira

  Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

• ARAI Yukinori

  Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.

• Matsukawa Utane

  Clinical Development Administration Development Astellas Pharma Inc.

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