生物活性

• 靶点

  Vasopressin Receptor 1A IC50:1.2μM

  Vasopressin Receptor 2A IC50:14nM

• 描述Arginine vasopressin (AVP) may contribute to cardiovascular regulation by causing vasoconstriction and stimulating renal water absorption through V1 and V2 receptors, respectively. Mozavaptan is a novel competitive vasopressin receptor antagonist for both V1 and V2 receptors with IC50 of 1.2 μM and 14 nM, respectively, with a V2:V1 receptor selectivity ratio of 25:1 and the binding to V1 and V2 receptors is competitive. After intravenous administration of Mozavaptan at doses of 10 to 100 μg/kg, the antidiuretic action of exogenous AVP was inhibited in a dose-dependent manner without decrease urine volume and water intake. In a clinical trial, 16 patients with Antidiuretic Hormone were researched about the clinical effectiveness of the vasopressin V2 receptor and they were given orally mozavaptan (single 30 mg tablet) once daily for 7 days. Serum sodium concentration increased at 24 h after the first administration of mozavaptan and remained elevated ≤24 h after administration for 7 days. ID 1 patient, a cancer-related patient was performed mozavaptan which was effective. But the condition became worse due to rapid tumor progression and the patient dead after 30 days post-treatment. During Phase I pharmacological evaluation, mozavaptan 30 mg/day exerted potent V2R antagonistic activity. Besides, mozavaptan improved compliance to chemotherapy in these patients and can be safely used in the target patient population, which is currently the only approved drug available for treatment of patients with ectopic ADH syndrome in Japan . Furthermore, with mozavaptan, according to a clinical trials, major side-effects were dry month (21%) and increases in aspartate aminotransferase, alanine transaminase, and serum potassium (7%) concentrations. Risk of excessive sodium correction or hypernatraemia exists with all the V2-receptor antagonists, if combined with fluid restriction.

• 动物研究
  剂量	Rat: 0.5 mg/kg - 10 mg/kg (i.p.); 1 mg/kg - 30 mg/kg (p.o.)
  给药途径	i.p., p.o.