Clonidine in the central nervous system: site and mechanism of hypotensive action

Abstract

The data presented in this paper must be considered in conjunction with the fact that clonidine is both a partial alpha-adrenergic agonist and a partial alpha-adrenergic antagonist. In the anterior hypothalamus, clonidine, acting as an alpha-agonist, excites a pathway that inhibits excitatory cardiovascular neurons. Thus, the effect of neurons from the nucleus tractus solitarii (NTS) in inhibiting sympathetic outflow from the vasomotor center is effectively increased. In the posterior hypothalmus, clonidine, acting as an alpha-antagonist, decreases excitation of excitatory cardiovascular neurons, or acting as an alpha-presynaptic agonist to decrease norepinephrine release, decreases excitation of excitatory cardiovascular neurons. Again the effect of neurons from the NTS in inhibiting sympathetic outflow from the vasomotor center is effectively increased. In the medulla, clonidine, acting as an alpha-antagonist, inhibits excitatory input to the sympathetic nervous system and thereby appears to enhance the excitatory vagal cardiac reflex and the inhibitory baroreceptor reflex. All of these actions produce the same final response: diminished sympathetic outflow from the CNS, which translates clinically into decreased arterial blood pressure. In addition, these sites and mechanisms of action provide a rational basis for the lack of orthostatic hypotension seen following clonidine and offer a possible mechanism of the post-treatment syndrome.