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.