Abstract
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.
Similar content being viewed by others
References
Bernard P, Bergen K, Sobiski R, Robson RD (1981) An orally effective benzodiazepine antagonist. Pharmacologist 23:150
Czernick AJ, Petrack B, Kalinsky HJ, Psychoyos S, Cash WD, Tsai C, Rinehart RK, Granat FR, Lovell RA, Brundish DE, Wade R (1982) CGS 8216: Receptor-binding characteristics of a potent benzodiazepine antagonist. Life Sci 30:363–372
File SE (1983) Proconvulsant action of CGS 8216. Neurosci Lett 35:317–320
File SE, Lister RG (1983a) Quinolines and anxiety: Anxiogenic effects of CGS 8216 and partial anxiolytic profile of PK 9084. Pharmacol Biochem Behav 18:185–188
File SE, Lister RG (1983b) Interactions of ethyl β-carboline-3-carboxylate and RO 15-1788 with CGS 8216 in an animal model of anxiety. Neurosci Lett 39:91–94
Greenblatt DJ, Matlis R, Abernethy DR, Ochs HR (1983) Improved liquid-chromatographic analysis of phenytoin and salicylate using radial compression separation. J Chromatogr 275:450–457
Hunkeler W, Möhler H, Pieri L, Polc P, Bonetti EP, Cumin R, Schaffner R, Haefely W (1981) Selective antagonists of benzodiazepines. Nature 290:514–516
Jensen LH, Petersen EN, Braestrup C (1983) Audiogenic seizures in DBA/2 mice discriminate sensitivity between low efficacy benzodiazepine receptor agonists and inverse agonists. Life Sci 33:393–399
Lister RG, Abernethy DR, Greenblatt DJ, File SE (1983) Methods for the determination of lorazepam and chlordiazepoxide and metabolites in brain tissue: A comparison with plasma concentrations in the rat. J Chromatogr 277:201–208
Lister RG, Greenblatt DJ, Abernethy DR, File SE (1984) Pharmacokinetic studies on RO 15-1788, a benzodiazepine receptor ligand, in the brain of the rat. Brain Res 290:183–186
Mendelson WB, Davis T, Paul SM, Skolnick P (1983) Do benzodiazepine receptors mediate the anticonflict action of pentobarbital? Life Sci 32:2241–2246
Yokoyama N, Ritter B, Neubert AD (1982) 2-Arylpyrazolo[4,3-c]quinolin-3-ones: Novel agonist, partial agonist, and antagonist of benzodiazepines. J Med Chem 25:337–339
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lister, R.G., Greenblatt, D.J. & File, S.E. A pharmacokinetic study of CGS-8216, a benzodiazepine receptor ligand, in the rat. Psychopharmacology 84, 420–422 (1984). https://doi.org/10.1007/BF00555224
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00555224