Effects of topiramate on sodium-dependent action-potential firing by mousespinal cord neurons in cell culture

Purpose: The effects of topiramate (TPM) on sodium-dependent action potenti als were studied by using cultured mouse spinal cord neurons. Methods: The ability of TPM to limit (block) depolarization-induced spontan eous repetitive firing (SRF) was determined and compared with corresponding effects of phenytoin (PHT) and lamotrigine (LTG) in cultured mouse spinal neurons. Results: Topiramate at concentrations of greater than or equal to 3 mu M ca used a voltage-sensitive and lime-dependent limitation of SRF that was asso ciated with a decrease in the velocity of the upstroke of the action potent ial. At high concentrations (30-600 mu M), TPM rapidly blocked SRF in about one third of the neurons tested and did not affect SRF in about one third. In some neurons, TPM caused an intermittent limitation (sputtering) of SRF (approximate to 30% of the neurons) or blocked SRF only after a delay of s everal seconds (approximate to 10%). This complex pattern of effects is dis tinctly different from that of PHT and LTG, in which the effect was always a rapid limitation or complete blockade of SRF. Another difference between TPM and the other anticonvulsants (AEDs) is that the effects of TPM were mo re dependent on the length of time the neurons were exposed to the compound and the intensity or duration of neuronal activity. Conclusions: The results of this study do not support the concept that Nat channel blockade is the primary mechanism responsible for the anticonvulsan t activity of TPM.