Dissociation of the effects of acute chlomipramine on morphine analgesia and plasma concentrations.

Morphine-induced analgesia and plasma concentrations were evaluated in rats after the administration of the opiate alone or together with chlomipramine, a tricyclic antidepressant drug. As expected, chlomipramine increased antinociceptive thresholds, but also increased morphine-induced analgesia in a dose-related fashion. Plasma concentrations of free morphine were higher in rats that had been administered chlomipramine, but the increase in plasma concentrations was not related to the increase in analgesic thresholds. In conclusion, the data reported indicate that chlomipramine increases the analgesic effect of morphine, but this is not related to plasma concentrations of the opiate.