L-740,093, a new antagonist of the CCK-B receptor, potentiates the antinociceptive effect of morphine: electrophysiological and behavioural studies.
The interaction between morphine and L740,093, a newly developed highly potent antagonist of cholecystokinin-B receptors, was examined in electrophysiological and behavioural studies. Intravenous L740,093 at 0.01 mg/kg had no effect on its own, but significantly potentiated the depressive effect of 1 mg/kg morphine on the nociceptive flexor reflex in decerebrate, spinalized rats. Similarly, subcutaneous L740, 093 at 0.03 mg/kg significantly prolonged the duration of antinociception induced by 10 mg/kg morphine in the rat hotplate test. A bell shaped dose-response curve was noted in the behavioural studies with respect to the interaction between L740,094 and morphine. L740,093, which has excellent CNS penetration, may represent a new tool in studying the involvement of the endogenous cholecystokinin system in the modulation of opioid analgesia and in exploring novel analgesics.
Xu
X J
XJ
Karolinska Institute, Department of Medical Laboratory Sciences and Technology, Huddinge University Hospital, Sweden.
Hoffmann
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O
Wiesenfeld-Hallin
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Z
D000698:Analgesia; D000701:Analgesics, Opioid; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001570:Benzodiazepinones / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D004594:Electrophysiology; D005260:Female; D007700:Kinetics; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010671:Phenylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*
D000701:Analgesics, Opioid; D001570:Benzodiazepinones; D010671:Phenylurea Compounds; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C090649:L 740093; D009020:Morphine