The influence of histamine receptor antagonists on antinociceptive action of narcotic analgesics.

The influence of some antagonists of histamine receptors on morphine-, fentanyl-, and pentazocine-induced analgesia was studied in rats and mice. H1-receptor antagonists (benzhydramine mepyramine) potentiated analgesic action of morphine and fentanyl. Given alone in high doses they also induced a naloxone non-reversible analgesia. Analgesic effects of pentazocine were not changed by benzhydramine and mepyramine. H2-receptor antagonist-cimetidine enhanced also analgesia induced by morphine and fentanyl in rats, but it either increased (after icv injection of 50 micrograms) or decreased (after icv injection of 100 micrograms) the action of pentazocine. Thus, H1 and H2 antagonists potentiate the antinociceptive effects of morphine and fentanyl but the action of pentazocine is not changed by H1 antagonists and is affected in an inconsistent manner by a H2 antagonist cimetidine. It seems that the potentiating effect of H-antagonists is related to the opioid mu receptors.