A novel kappa-opioid receptor agonist, TRK-820, blocks the development of physical dependence on morphine in mice.
The effects of a novel kappa-opioid receptor agonist, TRK-820, on the development of physical dependence on morphine were investigated in mice in comparison with those of U-50,488H. A marked body weight loss and several withdrawal signs were observed following naloxone challenge in morphine-dependent mice. Co-injection of TRK-820 (0.003-0.03 mg/kg, s.c.) but not U-50,488H (1-10 mg/kg, s.c.) during chronic morphine treatment dose-dependently suppressed the naloxone-precipitated body weight loss, jumping, wet dog shakes and diarrhea. These results suggest that TRK-820-sensitive kappa-opioid receptor subtypes may play a significant role in modulating the development of physical dependence on morphine.
Tsuji
M
M
Department of Pharmacology, Tokyo Medical College, Japan.
Takeda
H
H
Matsumiya
T
T
Nagase
H
H
Yamazaki
M
M
Narita
M
M
Suzuki
T
T
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism* / Q000517:prevention & control; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D013141:Spiro Compounds / Q000494:pharmacology*
D018712:Analgesics, Non-Narcotic; 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