Sites of action of alpha 2 agonists and antagonists

The alpha 2 adrenoceptor is found on central and peripheral neurons, on vascular smooth muscle and on endocrine tissue. Although some investigational drugs have widely varying affinities for these sites, clinically available alpha 2 agonists and antagonists act at all alpha 2 receptors. This report illustrates a strategy for evaluating the relative contributions of both central nervous system vs peripheral and of prejunctional vs postjunctional actions of a new drug by measurement of several alpha 2 receptor-mediated hemodynamic and neuroendocrine responses. Evidence is also provided for a temporal dissociation of pre- and postjunctional alpha 2 responses that may permit selective postjunctional alpha 2 blockade to be of clinical value in the treatment of sympathetically induced reductions of skin blood flow.