Effects of chlordiazepoxide, chlorpromazine, diazepam, diphenylhydantoin, flunitrazepam and haloperidol on the voltage-dependent sodium current of isolated mammalian brain neurons.

The effects of chlordiazepoxide, chlorpromazine, diazepam, diphenylhydantoin, flunitrazepam and haloperidol on the voltage-dependent sodium current (INa) were studied on the hippocampal pyramidal neurons, isolated acutely from rats, using a concentration clamp technique. The drugs used here reduced dose-dependently the peak amplitude of INa without affecting its current-voltage relationship. Chlorpromazine was most potent drug inhibiting the INa among them. Chlorpromazine and diphenylhydantoin at the concentration of half inhibition (IC50; 4 x 10(-6) M and 2 x 10(-4) M, respectively) shifted the steady state inactivation curve by more than 20 mV to a hyperpolarizing direction. Both drugs also caused a use-dependent inhibition of the INa. These results suggest that the drugs may block preferentially the inactivated sodium channels. While the concentrations of the drugs for inhibiting the INa are thought to be higher than those for affecting respective receptors for neurotransmitters, the results presented here may provide useful information to elucidate additional modes of action of these drugs in mammalian central nervous system.