Benzodiazepines produce contrasting effects on the active membrane properties of an invertebrate neuron

A perturbation of excitable membranes mediated by non-receptor (non-specific) mechanisms might be predicted from the hydrophobic nature of 1,4-benzodiazepines. Since correlations between membrane properties and neuronal effects have not been described for benzodiazepines, the effects of flurazepam, oxazepam and the benzodiazepine antagonist flumazepil (Ro 15-1788) were examined on both passive and active electrical properties of the membrane and neuronal discharge frequency. In this study, the isolated sensory neuron of the crayfish has been utilized as a neuronal model system. Flurazepam and flumazepil both enhanced the discharge frequency, in contrast to the depression produced by oxazepam. Discharge frequency was directly correlated with the maximum rate of rise of membrane potential during the threshold phase and was inversely correlated with spike threshold. In addition, the discharge frequency appeared to exhibit little dependence on peak amplitude, duration and the maximum rate of depolarization of the action potential. These findings are discussed in relation to non-specific mechanism(s) of action for benzodiazepines. It is suggested that, in the absence of a specific drug-receptor interaction, benzodiazepines in larger concentrations (greater than or equal to 50 mumol/l) exhibit selective membrane perturbations.