A pharmacokinetic study of CGS-8216, a benzodiazepine receptor ligand, in the rat.
A rapid and sensitive method is described for the determination of CGS-8216 (a pyrazoloquinoline that displaces benzodiazepines from their binding sites in the brain but which reverses some of the behavioural actions of the benzodiazepines) in plasma using high-performance liquid chromatography with ultraviolet detection. CGS-9896 serves as the internal standard. The method is applied to a pharmacokinetic study of CGS-8216 in the rat. CGS-8216 was not detectable in plasma 24 h after a single IP administration of a 10 mg/kg dose. Animals treated with five once-daily injections of CGS-8216 had plasma concentrations 30 min after the final injection that were approximately four-times those observed 30 min after a single treatment. This suggests that caution must be used in the interpretation of results from experiments using multiple administrations of CGS-8216. The compound could not be detected in brain tissue at any of the time points studied.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D003292:Convulsants / Q000494:pharmacology*; D007700:Kinetics; D011720:Pyrazoles / Q000097:blood* / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D003292:Convulsants; D011720:Pyrazoles; D011963:Receptors, GABA-A; C034704:2-(4-chlorophenyl)-2,5-dihydropyrazolo(4,3-c)quinoline-3(3H)-one; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one