Relative efficacies of benzodiazepine receptor agonists in affecting red nucleus electrical activity in rabbits.
The effects of benzodiazepine receptor agonists on the electrical activity of red nucleus (RN) and neocortex were studied in rabbits. Under basal conditions, 30-40 microV, 40-50 Hz waves were recorded in RN. An increase of the amplitude (Emax, 75-90 microV) was found after IV injection of flunitrazepam (ED50, 0.14 mg/kg), diazepam (ED50, 0.28 mg/kg), alpidem (ED50, 1.57 mg/kg) and zolpidem (ED50, 0.73 mg/kg). Clonazepam (ED50, 0.12 mg/kg) and Cl 218,872 (ED50, 0.63 mg/kg) were less effective. In contrast, 2-10-fold higher doses were required to induce a slight decrease of the frequency. At the level of the cortex all benzodiazepine agonists induced synchronization and spindles. The effects of diazepam (5 mg/kg IV) in both areas were antagonized by flumazenil (0.04 mg/kg IV) and bicuculline (0.2 mg/kg IV). Pentamethylentetrazole (10-30 mg/kg IV) selectively abated the effect at the level of the cortex, whereas both clonazepam (2 mg/kg IV) and beta-CCM (0.6 mg/kg IV) selectively suppressed only the effects on the RN. These results suggest that activation of benzodiazepine receptor mainly influences the RN waves amplitude. The efficacy in increasing the amplitude appears related to the reported relative efficacy of the compound in potentiating GABA responses. The possibility exists that these effects are dependent upon the partial or full agonist action of the drugs or upon their binding at distinct benzodiazepine receptor types.
Massotti
M
M
Laboratorio di Farmacologia, Istituto Superiore di Sanità, Roma, Italy.
De Medici
D
D
De Luca
C
C
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002998:Clonazepam / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D005445:Flunitrazepam / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D011724:Pyridazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D011963:Receptors, GABA-A / Q000187:drug effects*; D012012:Red Nucleus / Q000187:drug effects*; D000077334:Zolpidem
D007093:Imidazoles; D007546:Isoquinolines; D011724:Pyridazines; D011725:Pyridines; D011963:Receptors, GABA-A; D005442:Flumazenil; D002998:Clonazepam; D005445:Flunitrazepam; C021604:CL 218872; D000077334:Zolpidem; C052036:alpidem; D003975:Diazepam; D010433:Pentylenetetrazole; D001640:Bicuculline; C037850:PK 11195