Adrenergic receptors: biphasic dose responses.

Agonists and antagonists of the adrenergic receptor system were assessed for their capacity to affect dose-response relationships across biological model, tissue and endpoint. U shaped dose responses were commonly reported, affecting multiple endpoints such as smooth muscle contraction/relaxation, memory, blood pressure, sexual behavior, platelet aggregation, and others. In six of the endpoints studied, mechanistic foundations of the biphasic nature of the dose response were established. The quantitative features of the dose-response relationships indicated that the maximum stimulatory responses, with but one exception, were less than twofold greater than the controls. The range of stimulatory responses was generally within 10- to 1000-fold, except for the platelet aggregation endpoint where the range was 10(3) to 10(5).