Triazolam is more efficacious than diazepam in a broad spectrum of recombinant GABAA receptors.
Benzodiazepine-induced modifications of GABA (gamma-aminobutyric acid) activated Cl- currents were studied in native GABAA receptors expressed in neonatal rat brain cortical neurons in primary cultures and in recombinant GABAA receptors expressed in transformed human embryonic kidney cells (293) after a transient transfection with cDNAs encoding for different molecular forms of alpha, beta, and gamma subunits of GABAA receptors. The efficacy of triazolam in cortical neurons was higher than that of diazepam. In transfected cells, triazolam showed a greater efficacy as a positive modulator of GABA-elicited Cl- currents in alpha 1 beta 1 gamma 1, alpha 1 beta 1 gamma 2, alpha 1 beta 1 gamma 3, alpha 6 beta 1 gamma 2 and alpha 1 beta 3 gamma 2 receptors than diazepam, except in alpha 3 beta 1 gamma 2 receptors where diazepam was more efficacious. When triazolam and diazepam were applied together to GABAA receptors assembled by transfecting cDNAs encoding for alpha 1 beta 1 gamma 1 subunits, the action of triazolam was curtailed in a manner related to the dose of diazepam. In recombinant receptors assembled with alpha 1 beta 1 gamma 1 receptors, maximally active doses of triazolam were more efficacious than those of clonazepam, alpidem, zolpidem, diazepam or bretazenil.
Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, DC 20007.
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D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology*; D006801:Humans; D007668:Kidney; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014229:Triazolam / Q000494:pharmacology*
D018118:Chloride Channels; D002712:Chlorides; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D011994:Recombinant Proteins; D014229:Triazolam; D003975:Diazepam