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

The inhibitory effects of κ-opioid receptor agonists on systemic skin scratching induced by the intravenous administration of morphine, a μ-opioid receptor agonist, were investigated in rhesus monkeys. Intravenous pretreatment with κ-opioid receptor agonists, either TRK-820 at 0.25 and 0.5 μg/kg or...

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Published inLife sciences (1973) Vol. 75; no. 24; pp. 2947 - 2957
Main Authors Wakasa, Yoshio, Fujiwara, Atsushi, Umeuchi, Hideo, Endoh, Takashi, Okano, Kiyoshi, Tanaka, Toshiaki, Nagase, Hiroshi
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Inc 29.10.2004
Subjects
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - administration & dosage
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - therapeutic use
Animals
Dose-Response Relationship, Drug
Macaca mulatta
Morphinans - administration & dosage
Morphinans - therapeutic use
Morphine
Morphine - adverse effects
Motor Activity - drug effects
Observation
Pruritus - chemically induced
Pruritus - drug therapy
Receptors, Opioid, kappa - agonists
Rhesus monkeys
Scratching
Spiro Compounds - administration & dosage
Spiro Compounds - therapeutic use
Statistics, Nonparametric
TRK-820
U-50488H
TRK-820
Morphine
U-50488H
Scratching
Rhesus monkeys
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Summary:The inhibitory effects of κ-opioid receptor agonists on systemic skin scratching induced by the intravenous administration of morphine, a μ-opioid receptor agonist, were investigated in rhesus monkeys. Intravenous pretreatment with κ-opioid receptor agonists, either TRK-820 at 0.25 and 0.5 μg/kg or U-50488H at 64 and 128 μg/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 μg/kg but not with U-50488H from 512 to 2048 μg/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.
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2004.05.033