The novel kappa-opioid receptor agonist TRK-820 has no affect on the development of antinociceptive tolerance to morphine in mice.
The effects of the novel kappa-opioid receptor agonist 17-cyclopropylmethyl-3,14beta-dihydroxy-4, 5alpha-epoxy-6beta-[N-methyl-trans-3-(3-furyl)acrylamido+ ++]morphinan hydrochloride (TRK-820) on the development of antinociceptive tolerance to morphine were investigated in mice and compared with those of trans-3,4-dichloro-N-(2-(1-pyrrolidinyl)-cyclohexyl) benzenacetamide methane sulfonate hydrochloride (U-50,488H), a well-defined exogenous kappa-opioid receptor agonist. Morphine (1. 25-20 mg/kg, s.c.) produced a dose-related antinociceptive effect in the 51 degrees C warm-plate test. Daily treatment with morphine (10 mg/kg, s.c.) resulted in the development of antinociceptive tolerance. The development of antinociceptive tolerance to morphine was dose-dependently suppressed by the co-administration of U-50, 488H (1-10 mg/kg, s.c.) with morphine, but not TRK-820 (0.003-0.03 mg/kg, s.c.). These results suggest that TRK-820-sensitive kappa-opioid receptor subtypes may not be involved in modulating the development of antinociceptive tolerance to morphine.
Tsuji
M
M
Department of Pharmacology, Tokyo Medical College, Shinjuku-ku, Tokyo, Japan.
Yamazaki
M
M
Takeda
H
H
Matsumiya
T
T
Nagase
H
H
Tseng
L F
LF
Narita
M
M
Suzuki
T
T
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000502:physiology; D013141:Spiro Compounds / Q000494:pharmacology*
D000701:Analgesics, Opioid; D009019:Morphinans; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine