Multiple actions of picomolar concentrations of flurazepam on the excitability of cultured mouse spinal neurons.

Intracellular recordings from mouse spinal neurons grown dissociated in tissue culture were used to study the effects of the water soluble benzodiazepine, flurazepam, upon neuronal excitability. Low concentrations of this drug (1 pM to 10 nM) depressed excitability in three distinctly different ways: (1) by directly increasing Cl- conductance, (2) by potentiating responses to GABA, and (3) by elevating spike threshold and/or depressing repetitive spike firing. Bathing neurons with picrotoxin induced 'convulsive-like' activity which was attenuated by flurazepam. The direct effects of flurazepam on the passive and active properties of membrane excitability were insensitive to picrotoxin. However, when the dose of flurazepam was increased to 10 nM or greater this drug lost its effectiveness. These results show that flurazepam is a potent drug with multiple sites of action all of which are likely to contribute to its pharmacological actions in vivo.