| Abstract: |
Pretreating rats 24 h earlier with naloxonazine (10 mg/kg i.v.) virtually eliminates the analgesic response observed with morphine at 3.5 mg/kg (i.v.) and significantly reduces the elevation in tail-flick latencies seen with higher morphine doses. Full dose-response curves show a 4-fold shift to the right (P < .001) following naloxonazine treatment. At 3.5 mg/kg (i.v.), morphine depresses respiratory function, as determined by arterial blood gas (pO2, pCO2 and pH) measurements. Unlike analgesia, prior treatment of rats with naloxonazine does not alter the respiratory depressant actions of morphine. This inability of naloxonazine to antagonize the respiratory depressant actions of morphine is supported by full dose-response curves. Thus, prior treatment of rats with the mu-1-selective antagonist naloxonazine selectively antagonizes analgesia without affecting respiratory depression, implying different receptor mechanisms for the analgesic and respiratory depressant effects of morphine. Further comparisons of the analgesic and respiratory depressant effect of morphine and two opioid peptides, metkephamid and D-Ala2-D-Leu5-enkephalin, strongly suggest the involvement of mu-2 rather than delta mechanisms in opioid respiratory depression. |
| Keywords: |
drug efficacy; nonhuman; animal; animal experiment; dose-response relationship, drug; rat; rats; morphine; respiration depression; respiration; arterial gas; analgesia; intravenous drug administration; naloxone; opiate receptor; blood gas; blood gas analysis; drug interaction; naloxonazine; respiratory system; rats, inbred strains; receptors, opioid; male; priority journal; enkephalin, leucine-2-alanine; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; enkephalins; enkephalin, leucine; enkephalin[2 alanine 5 leucine]; metkephamid; blood and hemopoietic system; enkephalin, methionine
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