Opiates: Biphasic dose responses

It was shown that biphasic responses are commonly reported for opiates with respect to a broad range of animal models and endpoints. These endpoints i nclude such diverse functions as blood pressure, muscle tension, breathing rates, hCG production, HIV production, neutrophil migration, ACTH productio n, protein binding, and neuronal functioning. Quantitative features of the dose-response relationships indicated that the maximum stimulatory response s were less than or equal to 3-fold greater than the controls with most bei ng between 10 to 70% greater than the controls. In contrast to the striking similarity in the maximum stimulatory response, there was marked variation with respect to the dose range of the stimulatory responses that varied fr om 10(1) to 10(10). Mechanistic assessments were conducted for most biphasi c dose-response relationships and are addressed in detail.