Evidence for excitatory and depressant non-receptor-mediated membrane effects of benzodiazepines in the crayfish.

Oxazepam produced a significant reversible monophasic concentration-dependent (50-500 mumol/l) depression of stretch-induced discharge frequency of the isolated crayfish sensory neuron. In total contrast, flurazepam (10-200 mumol/l) evoked reversible excitation of the neuronal firing rate but at concentrations greater than 300 mumol/l it induced transient excitation followed by secondary total depression. The benzodiazepine antagonist flumazepil (less than or equal to 1 mmol/l) also produced an inherent increase in neuronal discharge frequency, though respective concentrations of 50 and 100 mumol/l failed to block flurazepam-excitation or oxazepam-depression. It is suggested that these high concentration qualitatively divergent neuronal effects are not mediated through specific benzodiazepine receptors.