Stereospecific effects of a kappa-opiate antagonist on the actions of morphine in morphine-tolerant rats.
The effects of kappa-opiate receptor antagonist, MR 2266 and its dextro isomer, MR 2267 on morphine-induced analgesia and changes in colonic temperature were determined in morphine-naive and morphine-tolerant male Sprague-Dawley rats. Intraperitoneal administration of morphine (8 mg/kg) produced analgesia and hyperthermia in morphine-naive rats. MR 2266 (0.3-3.0 mg/kg) antagonized morphine-induced analgesia and hyperthermia in morphine-naive rates but MR 2267 was inactive. Subcutaneous implantation of six morphine pellets during a 7 day period induced tolerance to the analgesic and hyperthermic effects of morphine in the rat. MR 2266 also antagonized morphine analgesia and hyperthermia in morphine-tolerant rats, however, MR 2267 had no effect. A high dose (3 mg/kg) of MR 2266 produced an intense hypothermic response in morphine-tolerant rats. Previously we have shown that kappa-opiate receptor agonists antagonize morphine analgesia in morphine-naive rats but potentiate it in morphine-tolerant rats. The results of the present studies indicate that the antagonist of kappa-opiate receptors, on the other hand, antagonize morphine effects in both morphine-naive and morphine-tolerant rats in a stereospecific manner.
Bhargava
H N
HN
Department of Pharmacodynamics, University of Illinois, Chicago 60612.
Kremer
E K
EK
Gibbons
M O
MO
Philips
B J
BJ
Driver
J W
JW
Chou
M
M
D000698:Analgesia; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D001831:Body Temperature / Q000187:drug effects; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D011957:Receptors, Opioid / Q000378:metabolism*; D017473:Receptors, Opioid, kappa; D013237:Stereoisomerism
D001575:Benzomorphans; D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C027247:MR 2266; D009020:Morphine