Respiratory depression after intravenous administration of delta-selective opioid peptide analogs.
We compared the effects of three micro-(DAMGO, DALDA, TNPO) and three delta-(DPDPE, DELT, SNC-80) opioid agonists on arterial blood gas after IV administration in awake sheep. None of the mu agonists altered pO2, pCO2 or pH. All three mu agonists decreased pO2 increased pCO2 and decreased pO2, and this effect was not sensitive to naloxone or TIPPpsi, a delta-antagonist, suggesting that it is not mediated by beta-opioid receptors. When administered to pregnant animals, there were significant changes in fetal pCO2 and pH. It may be possible to develop delta-selective opioid agonists which do not produce respiratory depression.
Szeto
H H
HH
Department of Pharmacology, Cornell University Medical College, New York, NY 10021, USA. hhszeto@mail.med.cornell.edu
Soong
Y
Y
Wu
D
D
Olariu
N
N
Kett
A
A
Kim
H
H
Clapp
J F
JF
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D007275:Injections, Intravenous; D010879:Piperazines / Q000494:pharmacology*; D011247:Pregnancy; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects*; D012756:Sheep
D000700:Analgesics; D001549:Benzamides; D004745:Enkephalins; D010879:Piperazines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D020881:Enkephalin, D-Penicillamine (2,5)-