TEMPORAL FACTORS IN THE ENHANCEMENT OF MORPHINE ANALGESIA BY DESIPRAMINE

Administration of desipramine, the tricyclic noradrenergic agent, for 7 days pre-operatively, had been found to potentiate postoperative mor phine analgesia. In this study we investigated the necessary timing of administration of desipramine in its action to potentiate morphine an algesia. We report that the administration of desipramine for only 3 d ays, starting 7 days before surgery, also potentiated postoperative mo rphine analgesia and that the analgesia observed was not different fro m that in patients receiving a full 7 days of desipramine pre-operativ ely. The potentiation of morphine analgesia observed was most evident as a prolongation of the analgesic response. Patients who also receive d desipramine for only 3 days, but starting 3 days pre-operatively had an analgesic response to postoperative morphine that was the same as that in patients receiving placebo. The ability of the administration of desipramine early in the pre-operative week to interact with postop erative morphine and the lack of response when desipramine was given l ate in the week does not have an explanation at present. However, it m ay reflect the known latency in humans to the onset of the central eff ects of tricyclic antidepressants (TCAs).