To investigate the effects of n-(2-propylpentanoyl) urea or valproyl urea (VPU) and valproic acid (VPA) , as a reference drug, on GABA[subscriptA] and glycine receptors in acutely dissociated rat hippocampal neurons using the whole-cell application of the patch clamp techniques. Concentration range of 1-300 micromolar, VPU did not directly induce inward currents in acutely dissociated rat hippocampal pyramidal neurones. The GABA[subscript A] currents could be enhanced by VPU, in a concentration-dependent manner, as well as pentobarbital sodium (PB) and diazepam (DZP). The GABA potentiating effect of VPU required higher concentration to reach the same potentiation effect in comparison to PB and DZP which had maximal potentiation effects at 300 micromolar and 1 micromolar, respectively. Valproic acid (VPA), a reference drug, did not directly elicite inward currents. However, at high concentration (30-5000 micromolar),VPA could potentiate the GABA[subscript A] currents with maximal potentiation effect at 4,000 micromolar. VPU and VPA did not affect the glycine currents. Flumazenil, a benzodiazepine antagonist, could not inhibit the potentiation of the GABA[subscript A] currents by VPU. However, VPU could inhibit the inward currents induced by PB. Moreover, coapplication of VPU with PB increased the potentiation of the GABA[subscript A] currents by each of these drugs applied with GABA. These results show that the effect of VPU on the GABA[subscript A] receptor may have some interaction directly or indirectly with the barbiturate site (s) on the GABA[subscript A] receptor channel. However, the clear mechanism(s) of the interaction need further investigation. The potentiation of the GABA[subscript A] currents by VPU may, at least in part, contributes to its mechanism of anticonvulsant action. The effects on other receptors involved in convulsion would also be interesting to investigate.