TRIAZOLAM IS MORE EFFICACIOUS THAN DIAZEPAM IN A BROAD-SPECTRUM OF RECOMBINANT GABA-A RECEPTORS

Benzodiazepine-induced modifications of GABA (gamma-aminobutyric acid) activated Cl- currents were studied in native GABA(A) receptors expressed in neonatal rat brain cortical neurons in primary cultures and in recombinant GABA(A) 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 GABA(A) 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 alpha1beta1gamma1, alpha1beta1gamma2, alpha1beta1gamma3, alpha6beta1gamma2 and alpha1beta3gamma2 receptors than diazepam, except in alpha3beta1gamma2 receptors where diazepam was more efficacious. When triazolam and diazepam were applied together to GABA(A) receptors assembled by transfecting cDNAs encoding for alpha1beta1gamma1 subunits, the action of triazolam was curtailed in a manner related to the dose of diazepam. In recombinant receptors assembled with alpha1beta1gamma1 receptors, maximally active doses of triazolam were more efficacious than those of clonazepam, alpidem, zolpidem, diazepam or bretazenil.