Antihypertensive action of indapamide and review of pharmacology and toxicology

Abstract

SummaryA series of studies was carried out to investigate the pharmacology and toxicology of indapamide. Indapamide decreased contractile responses of a number of different isolated vascular tissues to angiotensin, adrenaline and noradrenaline at concentrations of between 3 × 10-5M to 3 × 10-3M. Pre-treatment of normotensive rats for 6 days with indapamide 10 mg/kg or reserpine 0.5 mg/kg p.o. reduced by more than 50% the centrally-mediated pressor response to oxotremorine. At dose levels of up to 30 mg/kg i.v., indapamide failed to affect resting blood pressure in normotensive rats, cats and dogs. In DOCA-saline hypertensive rats, single oral doses of indapamide 1 mg to 100 mg/kg lowered systolic blood pressure by 10 to 35 mmHg for up to 96 hours. Treatment of DOCA-saline hypertensive rats for 2 weeks with indapamide 1 mg/kg p.o. produced a greater antihypertensive response than trichlormethiazide 3 mg/kg p.o. In spontaneously hypertensive rats, indapamide 3 mg to 30 mg/kg p.o. produced a reduction in blo...