No evidence for histamine-mediated morphine analgesia.

A role for brain histamine in the acute action of morphine was studied in mice. In contrast to earlier reports, whole brain histamine levels were not changed 30 min after morphine (1-56 mg/kg). Levels of the brain histamine metabolite, tele-methylhistamine were also unchanged. Morphine (1.8-10 mg/kg) caused a dose-dependent antinociceptive response that was unaffected by histamine H1-antagonists (i.p.), H2-antagonists (i.p. or i.vent.), or metoprine (i.p.), an inhibitor of histamine metabolism. alpha-Fluoromethylhistidine, the inhibitor of brain histamine synthesis, unexpectedly potentiated the response to low doses of morphine. These results find no evidence for a role of brain histamine in opiate analgesia.