Inhibitory effects of TRK-820 on systemic skin scratching induced by morphine in rhesus monkeys

摘要

The inhibitory effects of K-opioid receptor agonists on systemic skin scratching induced by the intravenous administration of morphine, a mu-opioid receptor agonist, were investigated in rhesus monkeys. Intravenous pretreatment with K-opioid receptor agonists, either TRK-820 at 0.25 and 0.5 mug/kg or U-50488H at 64 and 128 mug/kg, inhibited systemic skin scratching induced by morphine at 1 mg/kg, i.v. in a dose-dependent manner. By the intragastric route, apparent inhibitory effects on morphine-induced systemic skin scratching were evident following pretreatment with TRK-820 at 4 mug/kg but not with U-50488H from 512 to 2048 mug/kg. These results suggest that TRK-820 produces antipruritic effects on i.v. morphine-induced systemic skin scratching and is more readily absorbed intragastrically than is U-50488H, resulting in high bioavailability in the intragastric route. (C) 2004 Elsevier Inc. All rights reserved.