• J F Foss, E Orelind, and L I Goldberg.
• Committee on Clinical Pharmacology, University of Chicago, IL 60637, USA.
• Life Sci. 1996 Jan 1;59(15):PL235-8.

AbstractWe 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.

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