The Antihypertensive Effects of Ketanserin (R 41 468), a Novel 5-Hydroxytryptamine-Blocking Agent, in Patients with Essential Hypertension

Abstract

1. In a double-blind placebo-controlled crossover study a 4 week treatment with ketanserin was shown to reduce systolic and diastolic blood pressure markedly and significantly in 10 patients with essential hypertension. Heart rate remained virtually unchanged during the whole observation period. Systolic time intervals, reflecting cardiac output, did not change during the ketanserin phase, whereas these values deteriorated during the placebo period.2. Ketanserin, a novel 5-hydroxytryptamine (5HTJ-receptor antagonist with a high selectivity for blood vessels and thrombocytes, most probably acts by decreasing the venous capacitance bed constriction, and by counteraction of the amplifying effects of serotonin on noradrenaline and other vasoactive amines.

Ketanserin in essential hypertension: a double-blind, placebo-controlled study

“…This hypothesis has emerged largely from in vitro work as 5HT has had variable and inconsistent effects on blood pressure in both animals and man (Garrattini & Valzelli,, 1965). The recent characterization of 5HT2 receptors (Petroutka & Snyder, 1979) was followed by the development of a selective 5HT2 receptor antagonist, ketanserin (DeCree et al, 1981). This drug has made possible a closer examination of the role of 5HT in the maintenance of blood pressure.…”

“…This drug has made possible a closer examination of the role of 5HT in the maintenance of blood pressure. In initial open studies ketanserin appeared to lower blood pressure (DeCree et al, 1981;Wenting et al, 1982), and we have therefore performed a placebo-controlled study to establish that the drug has an antihypertensive effect. We also wished to evaluate its side effect profile and to assess the effectiveness of a twice daily dosage schedule.…”

Acute and chronic ketanserin in essential hypertension: antihypertensive mechanisms and pharmacokinetics.

“…Ketanserin is a selective 5-hydroxytryptamine (5-HT2) antagonist (Van Neuten et al, 1981;Leyson et al, 1981) which, either as monotherapy or in combination with a 1-adrenoceptor antagonist (De Cree et al, 1981;Hedner & Persson, 1985) has been shown to lower blood pressure in patients with essential hypertension. There is evidence that the antihypertensive effect of ketanserin is associated with a reduction in peripheral vascular resistance (Fagard et al, 1984) but the principal underlying mechanism remains to be established.…”

Chronic effect of ketanserin in mild to moderate essential hypertension.

“…A reduction of approximately 10% in cuff pressure has been reported in a double-blind placebo-controlled study of 10 patients using ketanserin, 20 mg t.i.d., 16 in a similar study of 8 patients using ketanserin, 40 mg b.i.d.,' 7 in a dose-finding study of 16 patients using ketanserin in an average daily dosage of 91 mg,' 8 and in a single-blind study of 13 patients receiving 40 mg once daily and 12 patients receiving 40 mg b.i.d. ' 9 A somewhat lower pressure reduction has been observed in a double-blind placebo-controlled crossover study of 14 patients receiving ketanserin, 40 mg t.i.d.…”