Effects of nor-binaltorphimine on the development of analgesic tolerance to and physical dependence on morphine.
The effects of a highly selective kappa antagonist, nor-binaltorphimine (nor-BNI), on the development of tolerance to morphine analgesia and physical dependence on morphine were examined. Pretreatment with nor-BNI (5 mg/kg s.c.) 2 h prior to injection of morphine or a selective kappa agonist, U-50,488H, significantly antagonized the analgesic effect of U-50,488H, but not morphine analgesia in mice. The development of tolerance to morphine analgesia was significantly potentiated by pretreatment of mice with nor-BNI 2 h prior to morphine treatment during chronic morphine treatment for 5 days. Additionally, the pretreatment with nor-BNI during chronic treatment with the high dose of morphine for 5 days significantly potentiated the naloxone-induced body weight loss in morphine-dependent mice and rats. These findings suggest that inactivation of the kappa opioid system may potentiate the development of tolerance to morphine analgesia in mice and may aggravate the naloxone-precipitated body weight loss in morphine-dependent mice and rats.
Suzuki
T
T
Department of Applied Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Narita
M
M
Takahashi
Y
Y
Misawa
M
M
Nagase
H
H
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000698:Analgesia; D000700:Analgesics / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats
D000700:Analgesics; D011759:Pyrrolidines; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine