Effects of methylnaltrexone on morphine-induced cough suppression in guinea pigs.
We administered methylnaltrexone, a peripheral opioid receptor antagonist, to guinea pigs previously injected with morphine sulfate to determine whether the compound could block opioid-induced cough suppression without blocking antinociception. The effects of methylnaltrexone (2.0, 1.6, 0.8 mg/kg) and of naltrexone (0.32, 0.16, 0.02 and 0.01 mg/kg) were compared in animals who had been injected with morphine sulfate (8.1 mg/kg). At 2.0 mg/kg methylnaltrexone, number of coughs returned to baseline value and nociception remained unaffected. At the two higher doses of naltrexone (0.32 and 0.16 mg/kg), morphine-induced antitussive effect was blocked, but antinociception was reversed. Our results suggested that methylnaltrexone possesses opioid antagonist activity in receptors peripheral to the blood-brain barrier. Its peripheral activity makes methylnaltrexone a clinically interesting agent for maintaining the cough reflex in those who must take opioids for analgosia.
Foss
J F
JF
Committee on Clinical Pharmacology, University of Chicago, IL 60637, USA.
Orelind
E
E
Goldberg
L I
LI
D000698:Analgesia; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds
D000996:Antitussive Agents; D009292:Narcotic Antagonists; D000644:Quaternary Ammonium Compounds; C032257:methylnaltrexone; D009271:Naltrexone; D009020:Morphine