The antagonism of benzodiazepine withdrawal effects by the selective cholecystokininB receptor antagonist CI-988.
The ability of a selective cholecystokininB (CCKB) receptor antagonist, CI-988, to block benzodiazepine withdrawal effects was examined in mice. The discontinuation of twice daily administration of diazepam (1 mg kg-1, i.p.) induced withdrawal anxiogenesis and a proconvulsant effect. In contrast, no such effects were seen following withdrawal from similar administration of CI-988. However, CI-988 dose-dependently (0.001-1.0 mg kg-1, s.c.) antagonized both the anxiogenesis and the proconvulsant effect following diazepam-withdrawal.
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge.
L
L
Singh
M J
MJ
Field
C A
CA
Vass
J
J
Hughes
G N
GN
Woodruff
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D003975:Diazepam / Q000009:adverse effects*; D004334:Drug Administration Schedule; D007211:Indoles / Q000494:pharmacology*; D008027:Light; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000517:prevention & control*
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D007211:Indoles; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D008536:Meglumine; D003975:Diazepam