The role of mast cells in the genesis of acute manifestations following the intravenous injection of meperidine in dogs.

The effects of intravenous (iv) administration of the synthetic opioid analgesic meperidine in conscious dogs and their relation to histamine stored in mast cells were studied in comparison with those induced by compound 48/80, potent mast cell degranulator. When 48/80 (0.5 mg/ kg) and meperidine (10 mg/kg) were injected iv into conscious dogs, an acute brief period of yelling, flare reaction, scratching, hypersalivation, urination, defecation, and tachypnea occurred after a latency of 30-35 sec. In addition, meperidine-treated dogs showed marked sedation. Dogs whose histamine stores were depleted by 48/80 manifested none of those effects induced by meperidine except sedation. Likewise, pretreatment with meperidine prevented the effects of a subsequent injection of 48/80. Sedation appeared to be independent of the histamine-releasing effect of meperidine, whereas other effects elicited by its intravenous injection of the drug were suppressed by 48/80 and thus were probably mediated via released histamine. We concluded that the peripheral effects of meperidine show histamine dependency and mast cells are a potential important site for the peripheral actions of meperidine as well.