1. A whole-cell patch-clamp study of the effects of ambocarb, a novel nootropic beta-carboline, on sodium currents in rat acutely isolated hippocampal pyramidal neurons was performed. 2. Ambocarb potently and reversibly suppressed sodium currents in a concentration range of 3-300 mumol/L. The amount of block was dependent on the holding potential, with half-maximal inhibition values being 26 and 94 mumol/L at -80 and -120 mV, respectively. 3. Ambocarb induced a hyperpolarizing shift in the steady state availability curve, which indicates an increase in the proportion of inactivated sodium channels. This action is presumably mediated by promoting the development of inactivation and slowing the recovery of sodium channels from inactivation. 4. Because many neuroprotective drugs were shown to inhibit sodium currents, down-modulation of voltage-operated sodium channels that complements the known positive interaction of ambocarb and other related beta-carbolines with GABAA receptors may provide a promising strategy in the treatment of brain disorders associated with trauma and ischaemia.