CCK(B) antagonists protect against some aspects of the ethanol withdrawal syndrome.
Effects of the CCK(B) antagonists, CAM1028 and C1988, and the CCK(A) antagonist, CAM1481, were studied on the ethanol withdrawal syndrome. When handling-induced behavior was measured hourly for 12 h from withdrawal of ethanol, a small, but significant, protective effect was seen with 3 mg/kg CAM1028, but not with 0.3, 1, or 10 mg/kg. C1988 (0.3 1,3, or 10 mg/kg), or CAM1481 (0.1 or 1 mg/kg), had no effects. At 16 h from ethanol withdrawal, these ratings were significantly decreased by 3 mg/kg CAM1028 or C1988, but not by lower doses. At 16 h, CAM1481 had very small, but significant, protective effects. At 3 mg/kg, CAM1028, increased the latencies to audiogenic seizures, but had only small effects on convulsion incidence. CAM1481 did not alter the audiogenic convulsions. The decrease in convulsion thresholds to NMDLA, at 16 h from ethanol withdrawal, was completely prevented by CAM1028 or C1988, at 1 and at 3 mg/kg, but not by lower doses; CAM1481 had no significant effects. The results suggest change in CCK(B) receptors may be involved in the later stages of the ethanol withdrawal syndrome.
Wilson
J
J
Department of Pharmacology, School of Medical Sciences, Bristol, UK.
Little
H J
HJ
D000161:Acoustic Stimulation; D000437:Alcoholism / Q000503:physiopathology / Q000523:psychology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000009:adverse effects*; D004151:Dipeptides / Q000627:therapeutic use*; D000431:Ethanol / Q000009:adverse effects*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006234:Handling, Psychological; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D012640:Seizures / Q000503:physiopathology; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology
D014151:Anti-Anxiety Agents; C097931:CAM 1481; D002492:Central Nervous System Depressants; D004151:Dipeptides; D018690:Excitatory Amino Acid Agonists; D007211:Indoles; D011949:Receptors, Cholecystokinin; C065600:PD 135158; C065599:PD 134308; D000431:Ethanol; D016202:N-Methylaspartate; D008536:Meglumine