Potentiation of opioid analgesia by H1 and H2 antagonists

The finding that abusers of pentazocine and tripelennamine experience a heroin-like euphoria which neither drug alone can produce prompted this study on the possible potentiation of opioid analgesia by H-antagonists. The reaction to pain in seconds was assessed at the time of peak drug effect by measuring the latency to jump from a hot plate at 55 degrees C after drug administration in male Swiss Webster mice. Several H1 antagonists and the H2 antagonist cimetidine markedly potentiated analgesia of opioids (morphine, fentanyl and nalbuphine). No motor impairment occurred with any of the drugs and drug combinations at the doses studied. It is hypothesized that the H-antagonists may produce these effects by peripheral mechanisms or by a central action.