Mechanism of the antihypertensive effect of alpha 2-agonists.

Drugs such as clonidine, methyldopa, guanabenz, guanfacine, and lofexidine have their primary site of antihypertensive action in the central nervous system (CNS) to activate alpha 2-adrenergic receptors and lower arterial pressure. The most probable CNS site of action of these drugs is the medulla oblongata at a post-synaptic location. Current evidence indicates that within the medulla, the prototype drug, clonidine, most likely acts at the lateral reticular nucleus. This site is the most sensitive in terms of hypotension occurring after microinjection of clonidine. In addition, lesion of this nucleus abolishes the hypotensive effect of systemically administered clonidine. Recently, a clonidine-displacing endogenous brain substance has been isolated and partially purified from calf brain. Knowledge of where clonidine acts to lower blood pressure should help in assessing the role of an endogenous clonidine-displacing substance in CNS control of cardiovascular function.