EFFECTS OF METHYLNALTREXONE ON MORPHINE-INDUCED COUGH SUPPRESSION IN GUINEA-PIGS

We administered methylnaltrexone, a peripheral opioid receptor antagon ist, to guinea pigs previously injected with morphine sulfate to deter mine 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 high er doses of naltrexone (0.32 and 0.16 mg/kg), morphine-induced antitus sive 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 act ivity makes metylnaltrexone a clinically interesting agent for maintai ning the cough reflex in those who must take opioids for analgesia.