Lack of effect of flumazenil and CGS 8216 on the anxiolytic-like properties of loreclezole.
Loreclezole is a novel antiepileptic that interacts in a unique way with the GABAA receptor complex. Its anticonvulsant effect in rats is reversed by benzodiazepine receptor partial inverse agonists, such as CGS 8216 but not by the competitive benzodiazepine receptor antagonist, flumazenil (Ro 15-1788). In this study loreclezole (30.0-50.0 mg/kg i.p.) was found to induce an anxiolytic-like effect in a rat conditioned emotional response test that was reversed neither by flumazenil (10.0 mg/kg) nor by CGS 8216 (2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one, 0.3-3.0 mg/kg). The results suggest that the anxiolytic-like effects of loreclezole are not mediated by the benzodiazepine receptor.
Dawson
G R
GR
Merck, Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Curnow
R
R
Bayley
P
P
Rambridge
A
A
Tricklebank
M D
MD
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001569:Benzodiazepines / Q000037:antagonists & inhibitors; D003292:Convulsants / Q000633:toxicity*; D004347:Drug Interactions; D005442:Flumazenil / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D003292:Convulsants; D011720:Pyrazoles; D014230:Triazoles; D001569:Benzodiazepines; D005442:Flumazenil; C066440:loreclezole; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one