Naloxone reversal of opioid-induced respiratory depression with special emphasis on the partial agonist/antagonist buprenorphine.
Buprenorphine is relatively resistant to reversal by naloxone. We tested the effect of various doses and infusion schemes of naloxone on buprenorphine-induced respiratory depression and compared the data with naloxone-reversal of morphine and alfentanil-induced respiratory depression. Both morphine and alfentanil were easily reversed by low doses of naloxone (0.4 mg). Increasing doses of naloxone caused a bell-shaped reversal curve of buprenorphine with maximal reversal at naloxone doses between 2 and 4 mg. However, reversal was short-lived. The bell-shaped reversal curve may be related to the existence of two mu-opioid receptor subtypes, one mediating the agonist effects of opioids at low dose, the other mediating antagonistic effects at high dose.
Sarton
Elise
E
Leiden University Medical Center, Department of Anesthesiology, 2300 RC Leiden, The Netherlands. e.y.sarton@lumc.nl
Teppema
Luc
L
Dahan
Albert
A
D015760:Alfentanil / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005283:Fentanyl / Q000494:pharmacology*; D006801:Humans; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D051381:Rats; D015656:Respiratory Mechanics / Q000187:drug effects / Q000502:physiology*
D000701:Analgesics, Opioid; D015760:Alfentanil; D009270:Naloxone; D002047:Buprenorphine; D009020:Morphine; D005283:Fentanyl