title: Study of the Interaction of 1,4- and 1,5-Benzodiazepines with GABAA Receptors of Rat Cerebellum Granule Cells in Culture.
abstract: The effects of a classical 1,4-benzodiazepine agonist, such as diazepam, its catabolite N-desmethyl-diazepam (nordiazepam), and 1,5-benzodiazepines such as clobazam and RL 214 (a triazolobenzodiazepine previously synthesized in our labs) were evaluated on native GABAA receptors of cerebellar granule cells in culture. The parameter studied was the increase of GABA-activated chloride currents caused by these substances. The contributions of α6 β2/3 γ2 and α1 α6 β2/3 γ2 receptor subtypes to the increase of GABA-activated chloride current were investigated by comparing the effects of such substances in the presence vs. the absence of furosemide. Furosemide is in fact able to block such receptors. It was found that the percent enhancement of peak GABA-activated current doubled for diazepam, clobazam, and RL 214. However, it did not change for N-desmethyl-diazepam. These results indicate that diazepam, clobazam, and RL 214 interact exclusively with α1 β2/3 γ2 receptors, while N-desmethyl-diazepam seems to interact with not only α1- but also α6-containing receptors.
authors.affiliation: Dipartimento di Fisica, Università di Genova, Via Dodecaneso 33, 16146, Genova, Italy.
authors.forename: Periklis
authors.initials: P
authors.lastname: Nikas
authors.affiliation: Dipartimento di Fisica, Università di Genova, Via Dodecaneso 33, 16146, Genova, Italy. gatta@fisica.unige.it.
authors.forename: Elena
authors.initials: E
authors.lastname: Gatta
authors.affiliation: Dipartimento di Fisica, Università di Genova, Via Dodecaneso 33, 16146, Genova, Italy.
authors.forename: Aroldo
authors.initials: A
authors.lastname: Cupello
authors.affiliation: Dipartimento di Farmacia, Sezione Chimica Farmaceutica, Università di Genova, Genova, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Di Braccio
authors.affiliation: Dipartimento di Farmacia, Sezione Chimica Farmaceutica, Università di Genova, Genova, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Grossi
authors.affiliation: Dipartimento di Fisica, Università di Genova, Via Dodecaneso 33, 16146, Genova, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pellistri
authors.affiliation: Dipartimento di Fisica, Università di Genova, Via Dodecaneso 33, 16146, Genova, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Robello
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism*; D005665:Furosemide / Q000494:pharmacology; D058785:GABA-A Receptor Agonists / Q000494:pharmacology*; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D001569:Benzodiazepines; D005665:Furosemide