Antihypertensive action of indapamide and review of pharmacology and toxicology

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Abstract
A 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 blood pressure which was maximal at 15% to 20% after 24 hours. Indapamide was found to be approximately 30,100 and 300-fold more potent on blood pressure than frusemide, spironolactone and chlorthalidone respectively. Indapamide showed a prolonged saluretic activity at dose levels above 0.1 mg to 0.3 mg/kg p.o. in rats and dogs. It was more potent than hydrochlorothiazide but similar to the activity of clopamide. Investigations of other possible pharmacological actions proved negative. Toxicological studies showed a low order of toxicity for indapamide.

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