Enhancement of morphine analgesia by fenfluramine in subjects receiving tailored opioid infusions.

We evaluated the ability of fenfluramine, a serotonin releaser, to increase the analgesic potency of morphine administered by tailored i.v. infusion. Ten normal volunteers participated in 4 test sessions, involving different treatments on different days: (1) oral placebo/saline infusion, (2) oral placebo/morphine infusion, (3) oral fenfluramine (60 mg)/saline infusion, and (4) oral fenfluramine/morphine infusion. Subjects experienced repetitive painful dental electrical stimuli at strong but tolerable intensities during testing. On the 2 test days involving morphine, the opioid was administered by a computer-pump system that used individual pharmacokinetic parameters to achieve consecutive, steady plasma concentrations near target values of 16, 32 and 64 ng morphine/ml; each morphine concentration plateau was maintained for 45 min. On the saline infusion days, our procedures were identical to morphine test days except that the infused fluid contained no drug. For all sessions outcome measures included subject ratings of pain intensity, dental evoked potential (EP) amplitude, and visual analog scale (VAS) ratings of subjective side-effect intensities (nausea, alertness, dizziness, itching, mood). We obtained these measures during baseline and at each morphine concentration plateau or at corresponding times during saline infusions. Fenfluramine significantly increased the analgesic potency of morphine during the opioid infusion, while fenfluramine alone produced borderline analgesic effects. Fenfluramine alone decreased alertness slightly, but did not significantly increase morphine side effects. Thus, we conclude that fenfluramine enhances the analgesic potency of morphine without a parallel increase in opioid side-effect potency.