Effects of topiramate on sodium-dependent action-potential firing by mouse spinal cord neurons in cell culture.
The effects of topiramate (TPM) on sodium-dependent action potentials were studied by using cultured mouse spinal cord neurons.



The ability of TPM to limit (block) depolarization-induced spontaneous repetitive firing (SRF) was determined and compared with corresponding effects of phenytoin (PHT) and lamotrigine (LTG) in cultured mouse spinal neurons.



Topiramate at concentrations of > or =3 microM caused a voltage-sensitive and time-dependent limitation of SRF that was associated with a decrease in the velocity of the upstroke of the action potential. At high concentrations (30-600 microM), 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 (approximately 30% of the neurons) or blocked SRF only after a delay of several seconds (approximately 10%). This complex pattern of effects is distinctly 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 more dependent on the length of time the neurons were exposed to the compound and the intensity or duration of neuronal activity.



The results of this study do not support the concept that Na+ channel blockade is the primary mechanism responsible for the anticonvulsant activity of TPM.
McLean
M J
MJ
Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee 37212, USA.
Bukhari
A A
AA
Wamil
A W
AW
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077213:Lamotrigine; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010672:Phenytoin / Q000494:pharmacology; D015222:Sodium Channels / Q000187:drug effects*; D013116:Spinal Cord / Q000166:cytology / Q000196:embryology; D000077236:Topiramate; D014227:Triazines / Q000494:pharmacology
D000927:Anticonvulsants; D015222:Sodium Channels; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D010672:Phenytoin; D000077213:Lamotrigine