Centrally acting drugs in antihypertensive therapy.

The brain plays an important role in the regulation of blood pressure. Noradrenaline-containing cell bodies are present in several areas of the medulla. The nucleus of the solitary tract, an important centre for regulating baroreceptor and chemoreceptor reflexes, has a particularly rich innervation with adrenergic nerve endings. Stimulation of brain α-adrenoceptors by substances such as clonidine and methylnoradrenaline causes inhibition of the sympathetic outflow and a fall in the blood pressure, accompanied by dry mouth and sedation. Guanfacine is an α-adrenoceptor agonist with a pharmacological action which resembles that of clonidine but which enters the brain more slowly. A single dose of guanfacine 3 mg in normotensive volunteers had a similar hypotensive effect to clonidine 0.3 mg but the onset was delayed and the duration of action was greater. The maximum reduction of salivary flow was greater with clonidine than with guanfacine but the effect of guanfacine lasted longer. The peak sedation was similar with both drugs but the onset was slower and the duration was longer with guanfacine. The peak plasma concentration of guanfacine occurred from 1-4 h after the dose but the concentration at 1 h had reached 62% of the peak value. The mean plasma half-life was 12.2 h (range 9.4-15.3 h). The slow onset of action of both the hypotensive effect and the central side-effects of guanfacine despite rapid absorption of the drug into plasma suggests that peripheral effects upon presynaptic α-adrenoceptors do not play an important role in the action of drugs of this type.