CGS 20625 (2-(4-methoxyphenyl)2,3,5,6,7,8,9,10-octa hydrocyclohepta[b]pyrazolo-[3,4-d]pyridin-3-one) is a potent and selective
ligand for the central
benzodiazepine receptor (IC50 = 1.3 nM), with little or no affinity to several other
neurotransmitter receptor binding sites in vitro.
CGS 20625 had a
gamma-aminobutyric acid ratio of 0.9 and increased t-[35S]butylbicyclophosphorothionate binding by 20% in vitro, a profile indicative of a partial agonist or mixed agonist/antagonist. In vivo,
CGS 20625 blocked a
pentylenetetrazol discriminative cue with an ED50 = 1.7 mg/kg p.o. The compound selectively increased conflict responding in the Cook-Davidson paradigm with a minimal effective dose of 0.3 mg/kg p.o., as compared with 3.0 mg/kg p.o. for
diazepam. At doses as high as 100 mg/kg p.o.,
CGS 20625 had no effect on variable interval responding, suggesting minimal sedation. Unlike
diazepam,
CGS 20625 had no effect on rotorod performance at doses up to 100 mg/kg p.o. indicating no overt muscle relaxation, and did not potentiate the action of
ethanol in this behavioral paradigm. Also,
CGS 20625 had no marked effect on locomotor behavior, did not potentiate
hexobarbital sleep time and had no
sedative activity at doses up to 300 mg/kg p.o.
CGS 20625 was efficacious in preventing
pentylenetetrazol-induced
seizures (ED50 = 0.7 mg/kg p.o.), had less efficacy with no clear dose-response relationship against
picrotoxin-induced
seizures and had no effect on either
strychnine or electroshock-induced convulsions at doses up to 300 mg/kg p.o.(ABSTRACT TRUNCATED AT 250 WORDS)