Possible Interaction: Diazepam and Gamma-Aminobutyric Acid

“At the same time it strongly potentiated GABA currents via the binding site for diazepam in the transmembrane domain.”

“Impairment of lipid raft integrity by methyl-β-cyclodextrine (MβCD)-induced cholesterol depletion did not change the inhibitory effect of DMI at the NMDA receptor, whereas it enhanced the potentiating effect of Diaz at the GABAA receptor at non-saturating concentrations of GABA.”

“… GABA … diazepam the prevalence of the longest open-time component is increased from 13 ± 7 (mean ± SD, n = 5 patches) to 27 ± 8% (n = 3 patches) …:We conclude that benzodiazepines do not act by enhancing affinity of the orthosteric site for GABA but rather by increasing channel gating efficacy.”

“Benzodiazepines, such as Valium and Xanax®, stimulate GABA receptors, thus mimicking the calming effects of GABA but again do not fix the lack of GABA production.”

“The prototypic benzodiazepine, diazepam , potentiates responses to GABA in GABA(A) receptors that contain a gamma subunit.”

“The potency of GABA was characteristically increased by diazepam (1μM) in both receptor isoforms, but this increase was significantly greater (p<0.05) in receptors composed of α1β2γ2-subunits (approximately five-to sixfold) compared to α1γ2-subunits (∼2.2-fold).”

“Non-selective benzodiazepine (BZ) binding-site full agonists, exemplified by diazepam , act by enhancing the inhibitory effects of GABA at GABAA receptors containing either an α1, -2, -3 or -5 subunit.”

“GABA activated Cl(-)-currents were potentiated when DZ > 0.1 microM was added to non-saturating concentrations of GABA (< 0.1 mM GABA).”

“We conclude that prolongation of deactivation after application of GABA + DZ may be an important mechanism of the modulatory action of DZ at GABA(A) receptor channels.”

“In the … 10 microM gamma-aminobutyric acid (GABA) … of diazepam , flunitrazepam and midazolam to inhibit [3H]flumazenil binding to the alpha 1-construct were increased 3 to 5 fold, whereas …,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate methyl ester a 2.5-fold reduction in potency was observed.”

“These results are discussed in terms of gamma-aminobutyric acid (GABA) since it is known that diazepam enhances binding of GABA to its receptor and hence potentiates inhibitory effects of GABA in the spinal cord.”