Acute hemodynamic response to the S2-serotonergic receptor antagonist, ketanserin, in patients with primary pulmonary hypertension

doi:10.1016/0167-5273(87)90200-2

International Journal of Cardiology

Volume 14, Issue 3, March 1987, Pages 303-309

https://doi.org/10.1016/0167-5273(87)90200-2 Get rights and content

Abstract

The acute hemodynamic effect of intravenous ketanserin, an S₂-serotonergic receptor antagonist, was evaluated during right heart catheterization in 20 patients with primary pulmonary hypertension. Pulmonary and systemic vascular resistance and pressure and cardiac output were measured before and after infusion of low and high dose ketanserin. A small decrease in pulmonary vascular resistance occurred after high dose drug infusion (28.4 to 25.0 U · m²; P < 0.001), and mean pulmonary arterial pressure was unchanged. Decreases in systemic arterial pressure (91.9 to 85.9 mm Hg; P < 0.0005) and systemic resistance (46.2 to 38.6 U · m²; P < 0.001) were more pronounced. Cardiac index increased significantly (21.6 to 2.42 l/min/m²; P < 0.01) due to reduced ventricular afterload. This study indicates that ketanserin has a small pulmonary vasodilating effect in primary pulmonary hypertension of doubtful clinical significance, similar to conventional vasodilators.

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Of the 5-HT receptors, 5-HTR2A is dominantly expressed in vasculature, yet shows differential expression in pulmonary vessels or increase in PAH (Marcos et al., 2005). Early studies to assess Ketanserin efficacy as a 5HTR2A antagonist proved clinically effective in the treatment of systemic hypertension, yet could not be used in PAH due to the adverse effects of decreased systemic pressure (Mcgoon & Vlietstra, 1987; Frishman et al., 1995). A selective 5HTR2B antagonist (PRX-8066) was assessed in a two week randomized, double-blind Phase IIa trial in 72 patients with PAH associated with COPD.
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Ketanserin, a selective S₂-serotonin receptor blocker with α₁-adrenergic blocking effects, may be a suitable antihypertensive medication after coronary artery surgery and lacks side effects seen with other vasodilators. Fifty patients with systolic blood pressures greater than 150 mmHg after coronary artery surgery were given, in a randomized double-blind fashion, either ketanserin (K) or saline (S). Each patient received six successive boluses of 1 mL of S or 1 mL of K (5 mg) at 2-minute intervals. After the last injection, sodium nitroprusside was started whenever the systolic blood pressure exceeded 50 mmHg. In the K group, the following significant (P < 0.05) changes occurred: systolic and diastolic arterial pressure −12% and −11%, respectively; heart rate −3%; systolic and diastolic pulmonary artery pressure −5% and −6%; central venous pressure −5%; pulmonary capillary wedge pressure −5%; systemic vascular resistance −16%; pulmonary vascular resistance −8%; stroke index +6%. None of these parameters changed significantly in the S group. There was no change in pulmonary shunt fraction in either group. In the K group, five patients did not require any further antihypertensive therapy during the 120 minutes following the last bolus injection. Twenty patients needed sodium nitroprusside during this period. This occurred 37 minutes (±17 min) after the last bolus. In conclusion, after coronary artery bypass surgery, K is an effective antihypertensive medication, which does not cause reflex tachycardia or an increase in pulmonary shunt fraction. Exceeding the recommended dose of 10 (or 20) mg, as done in this study, does not seem to improve effectiveness or prolong the duration of action.

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^∗: Supported in part by American College of Cardiology/Merck-Sharp-Dohme Fellowship, 1982–83.

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Original studyAcute hemodynamic response to the S2-serotonergic receptor antagonist, ketanserin, in patients with primary pulmonary hypertension

Abstract

Primary pulmonary hypertension: current status

Modern Concepts Cardiovasc Dis

Characterization of the antihypertensive properties of ketanserin (R41468) in rats

J Pharmacol Exp Ther

Mechanism of the hypotensive effect of ketanserin

J Cardiovasc Pharmacol

Treatment of hypertension with ketanserin, a new selective 5-HT2 receptor antagonist

Br Med J

Original study
Acute hemodynamic response to the S₂-serotonergic receptor antagonist, ketanserin, in patients with primary pulmonary hypertension

Treatment of hypertension with ketanserin, a new selective 5-HT₂ receptor antagonist