title: Reversal of morphine, methadone and heroin induced effects in mice by naloxone methiodide.
abstract: Opioid overdose, which is commonly associated with opioid induced respiratory depression, is a problem with both therapeutic and illicit opioid use. While the central mechanisms involved in the effects of opioids are well described, it has also been suggested that a peripheral component may contribute to the effects observed. This study aimed to further characterise the effects of the peripherally acting naloxone methiodide on the respiratory, analgesic and withdrawal effects produced by various opioid agonists. A comparison of the respiratory and analgesic effects of morphine, methadone and heroin in male Swiss-Albino mice was conducted and respiratory depressive ED(80) doses of each opioid determined. These doses (morphine 9 mg/kg i.p., methadone 7 mg/kg i.p., and heroin 17 mg/kg i.p.) were then used to show that both naloxone (3 mg/kg i.p.) and naloxone methiodide (30-100 mg/kg i.p.) could reverse the respiratory and analgesic effects of these opioid agonists, but only naloxone precipitated withdrawal. Further investigation in female C57BL/6J mice using barometric plethysmography found that both opioid antagonists could reverse methadone induced decreases in respiratory rate and increases in tidal volume. Its effects do not appear to be strain or sex dependent. It was concluded that naloxone methiodide can reverse the respiratory and analgesic actions of a variety of opioid agonists, without inducing opioid withdrawal.
authors.affiliation: Department of Clinical and Experimental Pharmacology, 5th Floor Medical School North, University of Adelaide, Adelaide 5005, Australia. tanya.lewanowitsch@csiro.au
authors.forename: Tanya
authors.initials: T
authors.lastname: Lewanowitsch
authors.forename: John H
authors.initials: JH
authors.lastname: Miller
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Irvine
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D004347:Drug Interactions; D005260:Female; D003932:Heroin / Q000009:adverse effects; D008297:Male; D008691:Methadone / Q000009:adverse effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000009:adverse effects; D009270:Naloxone / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D010993:Plethysmography, Whole Body; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology / Q000627:therapeutic use; D012119:Respiration / Q000187:drug effects; D012131:Respiratory Insufficiency / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000517:prevention & control*
chemical_list: D000701:Analgesics, Opioid; D000644:Quaternary Ammonium Compounds; D009270:Naloxone; D003932:Heroin; C041269:N-methylnaloxone; D009020:Morphine; D008691:Methadone