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 include such diverse functions as blood pressure, muscle tension, breathing rates, hCG production, HIV production, neutrophil migration, ACTH production, protein binding, and neuronal functioning. Quantitative features of the dose-response relationships indicated that the maximum stimulatory responses were < or = 3-fold greater than the controls with most being 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 from 10(1) to 10(10). Mechanistic assessments were conducted for most biphasic dose-response relationships and are addressed in detail.