Ketanserin in essential hypertension: use as monotherapy and in combination with a diuretic or beta‐adrenoceptor antagonist.

Abstract

1 The antihypertensive efficacy and tolerability of twice-daily treatment with the 5-hydroxytryptamine antagonist ketanserin were examined in a double-blind, placebocontrolled trial of 7 weeks duration in 56 hypertensive patients. Twenty were untreated, 20 were already taking bendrofluazide 5 mg daily, and 16 were already taking atenolol 100 mg daily. Randomisation was stratified to compare ketanserin with placebo as monotherapy (n = 20), when added to bendrofluazide (n = 20), and when added to atenolol (n = 16). 2 The antihypertensive effect of ketanserin in all patients completing the study (mean daily dose 71 mg) was 10/6 mm Hg supine (P < 0.01/P < 0.01) and 6/6 mm Hg standing (NS/P < 0.01) when blood pressure was measured 2 h after the morning dose. Responses were similar in patients taking ketanserin as monotherapy, in addition to bendrofluazide, and in addition to atenolol, with reductions in mean arterial pressure of 4.6, 7.4 and 8.9 mm Hg respectively. 3 Ketanserin had no antihypertensive effect when measured 14 h after the last dose. The rise in blood pressure between 2 and 14 h after dosing was 11/4 mm Hg supine (P < 0.01/ NS) and 8/5 mm Hg standing (P < 0.05/P < 0.05). 4 The antihypertensive response to ketanserin was positively related to initial blood pressure and, independent of this, to age. It was not related to plasma concentrations of ketanserin or ketanserinol. 5 Five of 28 patients taking ketanserin discontinued treatment because of side-effects, compared with one of 28 patients taking placebo. Ketanserin treatment increased body weight by 1.0 kg (P < 0.05) and prolonged the corrected QT interval by 14 ms (P < 0.01). 6 Ketanserin has only modest antihypertensive efficacy when used as monotherapy, when added to a thiazide, or when added to a 13-adrenoceptor blocker. A twice-daily dosing regimen does not seem satisfactory.

Comparison of ketanserin, buspirone and propranolol on arousal, pupil size and autonomic function in healthy volunteers

“…Ketanserin is an anti-hypertensive agent with sympatholytic effects, via central 5HT2-mediated modulation of the sympathetic system (Cameron et al 1987). It is also an α 1 adrenergic and histamine receptor antagonist (Dollery 1999).…”

The effects of a 5‐HT2 receptor antagonist (ICI 169,369) on changes in waking EEG, pupillary responses and state of arousal in human volunteers.

“…These 5-HT2 receptors may be involved in the pathophysiology of CNS disorders such as anxiety, depression, schizophrenia and Parkinsonism (Cooper & Abbott, 1988). Outside the brain 5-HT2 receptors mediate a variety of functional responses, involving smooth muscle contraction, platelet aggregation and neuronal depolarisation, with possible involvement in such diseases as hypertension, coronary artery spasm, Raynaud's disease and migraine (Cameron et al, 1987;Davies & Steiner, 1990;De Clerck & Van Nueten, 1982;Hollenburg, 1988).…”

Pharmacokinetic-Pharmacodynamic Relationships of ??-Adrenoceptor Antagonists

“…17 (4) 1989. Although maximal blood pressure reductions have been correlated with peak plasma concentrations of the drug (Persson et al 1987), no direct relationship between ketanserin concentration and the fall in blood pressure has been described when group data are evaluated (Cameron et al 1987;Hedner et al 1986). …”