The CCK-B antagonist LY288513 blocks effects of diazepam withdrawal on auditory startle.
In order to explore the potential clinical utility of CCK-B antagonists for the treatment of benzodiazepine withdrawal symptoms, the auditory startle reflex was examined in rats undergoing withdrawal from the chronic administration of diazepam. Animals were exposed to diazepam continuously for 12 days (20 mg kg-1 per day) via osmotic minipumps. After 12 days the pumps were removed and the animals were allowed to go through spontaneous withdrawal for 4 days. Acute pretreatment with either diazepam or the selective CCK-B antagonist LY288513 dose-dependently blocked withdrawal-induced increases in the auditory startle response. These results support the hypothesis that the selective CCK-B antagonist LY288513 may be an effective treatment for alleviating at least some benzodiazepine withdrawal symptoms in man.
Rasmussen
K
K
Lilly Research Labs, Eli Lilly & Co., Indianapolis, IN 46285.
Helton
D R
DR
Berger
J E
JE
Scearce
E
E
D000161:Acoustic Stimulation; D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000502:physiology; D003975:Diazepam / Q000009:adverse effects*; D008297:Male; D011720:Pyrazoles; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D011720:Pyrazoles; C074681:1-(4-bromophenylaminocarbonyl)-4,5-diphenyl-3-pyrazolidinone; D002766:Cholecystokinin; D003975:Diazepam