Interaction of naloxone with mu- and delta-opioid agonists on the respiration of rats.
The respiratory depression induced by two mu-opiate agonists morphine and Tyr-D-Ala-Gly-N-Me-Phe-Met(O)-ol (FK-33824), and two delta-agonists Tyr-D-Ala-Gly-Phe-D-Leu (DADLE) and Tyr-D-Ser-Gly-Phe-Leu-Thr (D-Ser2-Thr6) was studied in rats by using the intracerebroventricular route. The four opioids caused a dose-dependent depression of respiratory frequency down to apnea but high doses of morphine elicited motor activation and seizure activity. FK-33824 was the most potent, followed by DADLE, D-Ser2-Thr6 and morphine. The in vivo apparent pA2 values were determined for naloxone against FK-33824, DADLE and D-Ser2-Thr6. The pA2 value of naloxone interacting with the mu-agonist FK-33824 was significantly lower than those obtained against the two delta-agonists. It is proposed that different types of opiate receptors are involved in the opiate-induced respiratory depression.
D000818:Animals; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D003864:Depression, Chemical; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D012119:Respiration / Q000187:drug effects*; D013997:Time Factors
D004745:Enkephalins; D009294:Narcotics; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D009020:Morphine