Antihypertensive therapy with ketanserin: metabolic and hemodynamic effects

Ketanserin, a serotonin-2-receptor antagonist, was administered to 12 subjects with mild to moderate hypertension in a randomized, double-blind, placebo-controlled crossover trial. After 6 weeks of ketanserin (40 mg every 12 h), blood pressures measured 12 h after dosing were not significantly different from those obtained during the placebo period. However, 2 h after ketanserin administration, supine systolic and diastolic blood pressures declined 11 +/- 10 mm Hg (p less than 0.01) and 6 +/- 5 mm Hg (p less than 0.005) from predose values, whereas placebo caused no change in either systolic or diastolic blood pressure. At the time of peak antihypertensive activity, plasma renin activity, aldosterone, growth hormone, and prolactin levels were unchanged. Prolactin levels decreased slightly (4.1 +/- 3.0 vs. 3.7 +/- 2.9 ng/ml, p less than 0.05) during ketanserin therapy when measured 12 h after dosing. Other pituitary hormones, serum testosterone, plasma catecholamines, and plasma lipids showed no changes. Heart rate was also unchanged. Stroke volume, measured 2 h after dosing, increased (70 +/- 22 vs. 85 +/- 31 ml, p less than 0.05) with ketanserin therapy, but cardiac output did not change significantly. Ketanserin has a moderate antihypertensive effect and neutral metabolic-hormonal profile when used as monotherapy for the treatment of hypertension. However, further studies are needed to define the frequency of dosing that will provide 24-h antihypertensive activity.