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 buprenorphineinduced 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 μ-opioid receptor subtypes, one mediating the agonist effects of opioids at low dose, the other mediating antagonistic effects at high dose.
KeywordsRespiratory Depression Hypoxic Ventilatory Response OPRM1 Gene Maximal Reversal Baseline Ventilation
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