Reversal of mu-opioid-mediated respiratory depression by alpha 2-adrenoceptor antagonism.
The present study was performed in order to evaluate the effects of the selective alpha 2-adrenoceptor antagonist 6-chloro-2,3,4,5-tetrahydro-3-methyl-1H-3-benzazepine (SK&F 86466) on dermorphin-induced analgesia, respiratory depression and inhibition of locomotor activity in the conscious rat. Intracerebroventricular (icv) administration of dermorphin (3 nmol/rat) decreased respiration rate and relative ventilatory minute volume maximally by 38% and 50% of baseline respectively. SK&F 86466 dose-dependently reversed the dermorphin-induced depression of ventilatory parameters, while SK&F 86466 exerted no effect on dermorphin-induced analgesia or depression of locomotor activity due to catalepsia. It appears, therefore, that alpha 2-adrenoceptors selectively interact with mu 2-opioid-receptor mediated effects, such as respiratory depression, but are not involved in the modulation of mu 1-opioid-related effects, such as supraspinal analgesia and depression of locomotor activity.
Vonhof
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Department of Neurology, F.E. Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Sirén
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D018847:Opioid Peptides; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu; D012119:Respiration / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D000701:Analgesics, Opioid; D001552:Benzazepines; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; C030058:dermorphin; C039139:benalfocin