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Inhibitory effects of TRK-820 on systemic skin scratching induced by morphine in rhesus monkeys
Yoshio Wakasa1, Atsushi Fujiwara, Hideo Umeuchi
1Pharmacology and Toxicology Department, Ina Research Inc., 2148-188 Nishiminowa, Ina, Nagano 399-4501, Japan. wakasa@ina-research.co.jp
Abstract:
The inhibitory effects of kappa-opioid receptor agonists on systemic skin scratching induced by the intravenous administration of morphine, a micro-opioid receptor agonist, were investigated in rhesus monkeys. Intravenous pretreatment with kappa-opioid receptor agonists, either TRK-820 at 0.25 and 0.5 microg/kg or U-50488H at 64 and 128 microg/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 microg/kg but not with U-50488H from 512 to 2048 microg/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.
Insights
Kappa-opioid receptor agonists, like TRK-820, effectively reduce scratching behaviors caused by morphine in rhesus monkeys. TRK-820 shows better absorption when given orally compared to U-50488H.
Area of Science:
- Pharmacology
- Neuroscience
- Primate Research
Background:
- Morphine, a micro-opioid receptor agonist, induces systemic skin scratching in rhesus monkeys.
- Kappa-opioid receptor agonists are investigated for their potential to counteract morphine-induced pruritus (itching).
Purpose of the Study:
- To evaluate the antipruritic effects of kappa-opioid receptor agonists (TRK-820 and U-50488H) on morphine-induced scratching in rhesus monkeys.
- To compare the efficacy of TRK-820 and U-50488H via intravenous and intragastric administration routes.
Main Methods:
- Rhesus monkeys were pretreated intravenously or intragastrically with varying doses of TRK-820 or U-50488H.
- Morphine was administered intravenously to induce systemic skin scratching.
- The inhibitory effects of the kappa-opioid receptor agonists on scratching behavior were quantified.
Main Results:
- Intravenous TRK-820 and U-50488H inhibited morphine-induced scratching in a dose-dependent manner.
- Intragastric TRK-820 (4 microg/kg) showed apparent antipruritic effects, while U-50488H (512-2048 microg/kg) did not.
- TRK-820 demonstrated greater efficacy and bioavailability via the intragastric route compared to U-50488H.
Conclusions:
- TRK-820 exhibits significant antipruritic effects against intravenous morphine-induced scratching.
- TRK-820 possesses superior intragastric absorption and bioavailability compared to U-50488H for managing morphine-induced pruritus.
