The Antihypertensive Effects of a Pure and Selective Serotonin-Receptor Blocking Agent (R 41 468) in Elderly Patients

Abstract

In a first experiment, an acute intravenous administration of 10 mg R 41 468, a pure serotonin-receptor blocking agent with high selectivity for blood vessels and thrombocytes and devoid of central effects, dramatically reduced systolic and diastolic blood pressure in 23 elderly hypertensive patients. Heart rate and cardiac output remained virtually unchanged. In a second double-blind placebo-controlled cross-over study a highly significant decrease of systolic and diastolic blood pressure was obtained in 14 elderly hypertensive patients during an 8-day oral treatment with 40 mg t.i.d. of R 41 468. No serious side-effects were observed. An oral maintenance therapy with R 41 468 for 3 weeks showed a further reduction of blood pressure, resulting in a normalization of blood pressure, taking into account the advanced age of the patients. R 41 468 most probably acts by decreasing the venous capacitance bed constriction. Essential hypertension might be causally related to an impairment of venous function, in which serotonin might be an important pressor factor.

In vivo and in vitro activity of selective 5‐hydroxytryptamine2 receptor antagonists

“…Considerable interest in the role of 5-HT in the control of blood pressure has arisen from numerous reports that have shown ketanserin to be an effective antihypertensive agent in various experimental animal models (Van Nueten et al, 1981a) and in man (De Cree et al, 1981). The proposal that 5-HT2 receptor blockade is responsible for the hypotensive effect of ketanserin is controversial, since ketanserin also possesses al-adrenoceptor blocking activity.…”

“…Ketanserin, a potent and selective inhibitor of binding at the 5-HT2 site (Leysen et al, 1981), is also able to inhibit the vasoconstrictor effects of 5-HT in a variety of isolated tissues at low concentrations (Van Nueten et al, 1981b). In addition, the observation that ketanserin is able to lower blood pressure in experimental animals (Van Nueten et al, 1981a;Persson et al, 1982) and in man (De Cree et al, 1981;Wenting et al, 1982) has renewed interest in the involvement of 5-HT in hypertension. However, the mechanism ofthe hypotensive effect of ketanserin remains controversial since ketanserin also possesses appreciable a,-adrenoceptor antagonist activity and it appears that the acute administration of ketanserin in rats produces a hypotensive effect at doses similar to those required to block a,-adrenoceptors (Fozard, 1982;Kalkman etal., 1982).…”

Ketanserin, a novel 5‐hydroxytryptamine antagonist: monotherapy in essential hypertension.

“…Ketanserin has also been shown to reduce blood pressure in man following acute treatment (DeCree et al, 1981;Wenting et al, 1982). The At steady state conditions (following at least 8 weeks of active treatment) plasma concentrations of ketanserin and blood pressure were determined during a 24 h period in a subpopulation of the study group (15 patients; 40 mg x 1, n = 5, 40 mg x 2, n = 10).…”

No Evidence for Serotonergic-Adrenergic Interactions in the Canine Total Cardiovascular System

“…Recent studies [Henry and Yokoyama, 1980;De Cree et al, 1981a;Demoulin et al. 1981;Wenting et al, 1982;Huval et al, 1983;Makabali et al, 1983] have stressed the importance o f serotonin in the pathophysiol ogy o f some cardiovascular disorders and hy pertension.…”