EVIDENCE FOR MU(1)-OPIOID RECEPTOR INVOLVEMENT IN FENTANYL-MEDIATED RESPIRATORY DEPRESSION

Several fentanyl analogs (Bagley et al., 1989, J. Med. Chem. 32, 663) were compared to fentanyl and morphine for their effects on respirator y depression as determined by arterial blood gas (pH, pCO(2) and pO(2) ) measurements. Fentanyl (0.1 mg/kg), morphine (10 mg/kg), #16 n-2-yl) -N-(methoxymethylcarbonyl)amino]piperidine, 1 mg/kg), #17 -4-[N-(pyrid in-2-yl)-N-(2-furoyI)amino]piperidine, 0.5 mg/kg) and #29 -yl)-N-(meth oxy-mehtylcarbonylyl)amino]piperidine, 10 mg/kg) produced significant respiratory depression in rats. Pretreatment with the mu(1)-opioid rec eptor selective antagonist, naloxonazine (10 mg/kg), blocked the respi ratory effect of fentanyl and its analogs, but not that of morphine. T he results suggest that the mu(1)-opioid receptor plays an important r ole in the respiratory effects of fentanyl and its analogs. Hence, the mechanism of fentanyl-induced respiratory depression appears to be di stinct from that produced by morphine. The most likely explanation for this difference is the possible contribution of muscle rigidity and c atalepsy to the observed changes in blood gas parameters caused by the fentanyl analogs, while the respiratory depression of morphine, measu red by these same parameters, appears to be independent of its effect on muscle rigidity.