Comparative effects of opioid peptides on respiration and analgesia in rats.
Receptor mechanisms for opiate induced respiratory depression and analgesia (tail-flick) were studied by the ED50 ratios and the apparent pA2 values of the interactions of naloxone with the mu-agonists morphine and D-ala2-me-phe4-met (O)ol5-enkephalin (FK-33824), and the delta-agonists D-ala2-D-leu5-enkephalin (DADL) and tyr-D-ser-gly-phe-leu-thr. The apparent pA2 values of morphine, FK-33824 and DADL for analgesia were similar, whereas the apparent pA2 values of the mu-agonists for respiratory depression were significantly lower than those of the delta-agonists. The ratio between the ED50 of FK-33824 in analgesia and respiratory depression was much lower than that of DADL. It is concluded that different receptors mediate the opiate-induced respiratory depression. One difficulty with the delta-receptors being maximally involved in this action is the high degree of antagonism shown by naloxone on the respiratory effects of the delta-agonists.
D000698:Analgesia; D000818:Animals; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D004723:Endorphins / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004745:Enkephalins / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*
D004723:Endorphins; D004745:Enkephalins; D011957:Receptors, Opioid; D009270:Naloxone; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D009020:Morphine