Guanfacine and other centrally acting drugs in antihypertensive therapy; pharmacological and clinical aspects.

Centrally acting antihypertensive agents exert an agonist action on alpha-adrenoceptors in certain areas of the brain, thereby reducing sympathetic outflow and lowering blood pressure without paralysing peripheral homeostatic control mechanisms. Some also stimulate peripheral alpha-adrenoceptors, both postsynaptic and presynaptic. Guanfacine, a representative member of this class of drugs, resembles clonidine in most of its basic pharmacological properties. In some respects, however, clear differences exist and may account for an improved therapeutic usefulness. In cats the two drugs have a different site of action within the CNS. Unlike clonidine, guanfacine does not inhibit dopamine turnover in the corpus striatum of the rat and its hypotensive effect is not inhibited by central H2-receptor blockade. In rat EEG studies guanfacine is much less sedative than clonidine. The newer drug shows a higher selectivity for (peripheral) presynaptic alpha-adrenoceptors than clonidine. On a weight basis guanfacine is about 10 times less potent in lowering blood pressure, but at equipotent doses its antihypertensive effect lasts longer. With an elimination half-life of approximately 18 to 21 h in man guanfacine is suitable for once-a-day treatment. The long duration of action is likely to explain the lack of rebound hypertension in chronically treated spontaneously hypertensive rats as well as the very low incidence and the remarkably mild nature of withdrawal symptomatology in man.