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Ageing, Serotonin and Ketanserin

Research paper by Alasdair Breckenridge

Indexed on: 18 Oct '12Published on: 18 Oct '12Published in: Drugs



Abstract

In both acute and long term clinical studies, the antihypertensive effects of the S2-serotonergic receptor antagonist ketanserin are more marked in the elderly than in younger patients. The acute effect of ketanserin 10mg intravenously was studied in 57 patients between 25 and 90 years and a significant negative correlation was shown between age and the decrease in both systolic and diastolic blood pressure. In longer term studies ketanserin has been compared with metoprolol and hydrochlorothiazide in patients below and above 60 years. Both ketanserin and the diuretic showed greater antihypertensive efficacy in the elderly, whereas the β-blocker did not. Data from 15 double-blind studies from the ketanserin International Data File confirm the relationship between age and antihypertensive efficacy.With respect to adverse effects of ketanserin, dizziness, somnolence and dryness of the mouth were commoner in younger than in older patients. These effects were not the result of smaller dose requirements in the elderly, and there was no obvious pharmacokinetic reason (e.g. alteration in drug clearance) for the difference.Two theoretical possibilities for the differential age effect of ketanserin are advanced. First the smaller effect in the young may be due to activation of homeostatic mechanisms limiting its antihypertensive activity, or second, some selective (undefined) effect operative in the elderly may be responsible. It is known from animal studies that serotonin shows increased vasoconstrictor properties in the presence of extensive atheroma. Antagonism of this effect may account for the greater vasodilator and antihypertensive effect of ketanserin in elderly patients. This, however, is speculative and does not take into account the complex antihypertensive action of ketanserin.The role of serotonin in cardiovascular control is complex. Its effects depend on the species studied, the vascular bed being investigated, the dose used and the experimental conditions employed. Serotonin has central cardiac and peripheral vascular actions relevant to cardiovascular control. In the peripheral vasculature it can produce vasodilatation or vasoconstriction by either direct or indirect mechanisms. If this complexity were not confusing enough, the nomenclature of the receptors on which serotonin acts is under intense current debate, and little uniformity exists as to the terminology to be used.The terms of this review will be very specific. The hypothesis is put forward that, on both theoretical and clinical grounds, the serotonin antagonist ketanserin lowers blood pressure more effectively in an older than a younger population and thus may have a therapeutic role in treating elderly hypertensive patients.