Possible Interaction: Gamma-Aminobutyric Acid and Midazolam

“The utility of this class of compounds relates to their ability to enhance both preand postsynaptic inhibition mediated by gamma-aminobutyric acid , the endogenous inhibitory neurotransmitter.2 It may be inferred that agents within the benzodiazepine class, including midazolam , would be effective in controlling SE.”

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

“ Midazolam exerts its action by enhancing the effects of γ-aminobutyric acid (GABA) on GABAa receptors, resulting in neural inhibition.”

“The ventilatory responses to sustained isocapnic hypoxia were studied in six adult male subjects on three separate days in three pharmacological conditions: (1) without any drug administration; (2) during infusion of midazolam (a drug which potentiates the effect of GABA ); and (3) during infusion of flumazenil (a benzodiazepine antagonist).”

“In HR animals, the pretreatment of rats with d-cycloserine and midazolam significantly increased the local concentration of GABA and inhibited the expression of contextual fear.”

“Conclusions Midazolam reduced excitatory synaptic transmission by acting on the & ggr;-aminobutyric acid type A/benzodiazepine receptor in interneurons, leading to a decrease in the excitability of spinal dorsal horn neurons.”

“Both blockers antagonized the QO2 reducing effect of the combination of per se effective doses of midazolam (1.0 mg/kg) and GABA (5 x 10(-4) mol/l), as well as of GABA (5 x 10(-4) mol/l) itself.”

“However, neither effects of midazolam (1.0 mg/kg) on its own, nor those of midazolam in presence of the physiological, per se ineffective, concentration of GABA (10(-6) mol/l), were susceptible to antagonism.”

“However, it completely antagonized effects of midazolam on QO(2), on its own and in presence of GABA.”

“In this report we examine the ability of midazolam to potentiate gamma-aminobutyric acid (GABA) mediated inhibition recorded from cerebellar Purkinje neurons using extracellular recording methods.”

“We report … when midazolam is applied concurrently with GABA from glass multibarrel electrodes that midazolam potentiates GABA mediated inhibition in 46% of Purkinje neurons in 3-month-old F344 rats, 63% of neurons in 18-month-old F344 rats and 54% of cells in 24-month-old F344 rats.”

“The benzodiazepine, midazolam , potentiated GABA currents to a greater degree in aged animals, consistent with previous reports of enhanced benzodiazepine activity with age.”