title: Cerebral-activating (EEG) properties of two inverse agonists and of an antagonist at the benzodiazepine receptor in the rat.
abstract: In order to assess the effects of inverse benzodiazepine agonists and antagonists on brain function, computerized EEG (CEEG) analysis was performed in rats following the i.p. administration of SR 95195 (7-phenyl-3-methyl-1,2,4 triazolo-[4,3-b]pyridazine) and CGS 8216 (2-phenylpyrazolo-[4,3c]-quinoline-3-[5H]-one) two benzodiazepine receptor inverse agonists (BRIAGs) and of flumazepil (Ro 15-1788), a benzodiazepine receptor antagonist (BRANT). The EEG effects of SR 95195 (3, 10, 30 and 60 mg/kg), CGS 8216 (10 and 30 mg/kg) and flumazepil (3, 10, 30 and 60 mg/kg) were compared to those of the psychostimulant drugs DL-amphetamine (0.1, 0.3 and 1 mg/kg), and caffeine (10 and 30 mg/kg) and those of aniracetam (100 and 300 mg/kg), a nootropic pyrrolidone derivative. The CEEG profiles of SR 95195, CGS 8216 and flumazepil were mainly characterized by a power increase in the 20-32 Hz frequency range and by a power reduction in the 8-16 Hz range. These effects were quite similar to those of the psychostimulants DL-amphetamine and caffeine as well as to those of the nootropic aniracetam. Other psychotropic drugs with CNS-depressant properties, namely diazepam (10 mg/kg p.o.), pentobarbital (30 mg/kg p.o.), chlorpromazine (10 mg/kg i.p.) and imipramine (10 mg/kg i.p.) induced quite different EEG power modifications. These results show that BRIAGs and BRANTs possess a marked intrinsic activity at the central level and suggest that this activity is CNS-activating in nature.
authors.affiliation: Department of Neuropsychiatry, Sanofi Recherche, Montpellier, France.
authors.forename: V
authors.initials: V
authors.lastname: Santucci
authors.forename: M
authors.initials: M
authors.lastname: Fournier
authors.forename: P
authors.initials: P
authors.lastname: Worms
authors.forename: P
authors.initials: P
authors.lastname: Keane
authors.forename: K
authors.initials: K
authors.lastname: Bizière
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004569:Electroencephalography; D005442:Flumazenil / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D000697:Central Nervous System Stimulants; D011720:Pyrazoles; D011724:Pyridazines; D011760:Pyrrolidinones; D011963:Receptors, GABA-A; C051712:7-phenyl-3-methyl-1,2,4-triazolo-(4,3b)pyridazine; D005442:Flumazenil; C036466:aniracetam; C033830:2-phenylpyrazolo(4,3-c)quinolin-3(5H)-one; D010424:Pentobarbital; D007099:Imipramine; D003975:Diazepam; D002746:Chlorpromazine