Recent developments in the pharmacology and pharmacokinetics of indoramin

Some recent studies complementing earlier reports on the pharmacology and pharmacokinetics of indoramin are briefly reviewed. Competitive blockade of peripheral postsynaptic alpha 1-adrenoceptors is confirmed as the primary mechanism for the antihypertensive activity of indoramin. Various reasons have been proposed to explain the absence of reflex tachycardia when blood pressure is reduced by indoramin. These have included myocardial membrane stabilization and selectivity for alpha 1-adrenoceptors. More recently, class III antiarrhythmic activity and a reduction in baroreceptor sensitivity have also been proposed, and several animal studies have indicated that a central cardioregulatory mechanism contributes to the lack of reflex tachycardia. Chronic dosing with indoramin in hypercholesterolemic monkeys significantly raises high-density lipoprotein cholesterol levels. Recent pharmacokinetic and biotransformation studies confirm earlier reports that the drug is well absorbed and extensively metabolized and has a plasma half-life of approximately 5 h. This is increased in the elderly. 6-Hydroxyindoramin is a major metabolite; it is pharmacologically very similar to indoramin itself, except that it penetrates the central nervous system less readily. Plasma levels of this metabolite are about one-third those of indoramin during chronic twice-daily dosing. Its formation is not expected to have any undesirable clinical consequences.