Ketanserin

Abstract

Ketanserin is a 5-HT2 receptor antagonist without partial agonist properties which also possesses weak alpha 1-adrenoceptor antagonistic activity, which may explain its antihypertensive mechanism of action in patients with essential hypertension. It also inhibits the effects of serotonin on platelets in cardiovascular disease, inhibits vasoconstriction caused by the amine, and when administered intravenously improves some haemorheological indices in patients with ischaemic diseases. The antihypertensive effect of oral ketanserin 40 mg twice daily is comparable with that of total daily doses of metoprolol 200 mg, propranolol 160 mg, captopril 100 mg, enalapril 20 mg, hydrochlorothiazide 50 mg, or alpha-methyldopa 1000 mg and is achieved without adverse effect on plasma lipoproteins or carbohydrate metabolism in patients with concomitant diabetes mellitus. Evidence from prospective studies suggests a greater antihypertensive efficacy in the elderly than in younger patients. In patients with intermittent claudication, results have been inconsistent in small studies, while a large study showed no improvement in pain-free walking distance but fewer amputations compared to placebo. In Raynaud's phenomenon symptomatic improvement relative to placebo was achieved in larger trials. Its role in preventing atherosclerotic complications requires further investigation. Ketanserin is reasonably well tolerated, the frequency of adverse effects being comparable with that of other antihypertensive drugs in controlled trials. Dizziness, tiredness, oedema, dry mouth and weight gain are the most commonly reported effects. Ketanserin prolongs QT interval in a dose-related manner, and when given in certain predisposing circumstances ventricular arrhythmias and syncope may occur. Administered intravenously, ketanserin 10mg followed by an infusion of 2 to 4 mg/h controls moderate to severe pre- and postoperative hypertension in most patients, acting as a balanced vasodilator, lowering cardiac pre- and afterload. Although the arrhythmogenic potential of ketanserin in patients receiving potassium-depleting diuretics requires suitable precautions, it appears that its antihypertensive activity is suited to the elderly provided plasma potassium concentrations are normal at the start of treatment and are maintained within the normal range.

MDMA-Induced Dissociative State not Mediated by the 5-HT2A Receptor

“…Pre-treatment consisted of ketanserin (40 mg), which represents a regular therapeutic dose that blocks 91% of 5-HT 2 receptors (Brogden and Sorkin, 1990; Sharpley et al, 1994), or placebo; Treatment consisted of MDMA (75 mg) or placebo. Pre-treatment and treatment were administered orally in identically appearing capsules using a double-blind, placebo-controlled, double-dummy procedure.…”

Effects of Acute MDMA Intoxication on Mood and Impulsivity: Role of the 5-HT2 and 5-HT1 Receptors

“…The 75 mg dose of (racemic) MDMA was selected because it falls within the normal range of recreational use [24] and has been consistently shown to impair performance and produce robust subjective mood changes in a number of previous studies from our group [31], [32], [33]. Doses of pindolol 20 mg and ketanserin 50 mg represent regular therapeutic doses that block approximately 40% of 5-HT 1A receptors and 91% of 5-HT 2 receptors respectively [34], [35], [36]. MDMA, pindolol and ketanserin were acquired through the local hospital pharmacy, which also performed randomization, capsulation and distribution of study drugs.…”

Effects of MDMA on body temperature in humans

“…However, in humans, ketanserin alone also reduced body temperature compared with placebo, and the effects with MDMA were therefore mostly additive 44 . Additionally, ketanserin has α 1 -adrenergic receptor-blocking properties 59 and may reduce peripheral vascular resistance and body temperature. The serotonin 5-HT 1A receptor antagonist pindolol did not alter the MDMA-induced increase in body temperature in humans, 60 also consistent with preclinical data 58 .…”