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Rawls, S.M. et al.

Scott M. Rawls, Timmy Thomas, Mobilaji Adeola, Tanvi Patil, Natalie Raymondi, Asha Poles, Michael Loo, Robert B. Raffa,

Topiramate antagonizes NMDA- and AMPA-induced seizure-like activity in planarians.

The mechanism of anticonvulsant action of topiramate includes inhibition of glutamate-activated ion channels. The evidence is most convincing for direct inhibitory action at the ionotropic AMPA (alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid) and kainate ((2S,3S,4S)-3-(Carboxymethyl)-4-prop-1-en-2-ylpyrrolidine-2-carboxylic acid) glutamate receptor subtypes. Less direct connection has been made to the NMDA (N-Methyl-d-aspartate) subtype. In the present study, we demonstrate that NMDA and AMPA produce concentration-dependent seizure-like activity in planarians, a type of flatworm which possesses mammalian-like neurotransmitters. In contrast, planarians exposed to the inhibitory amino acid, glycine, did not display pSLA. For combination experiments, topiramate significantly reduced planarian seizure-like activity (pSLA) produced by NMDA or AMPA. Additionally, NMDA-induced pSLA was antagonized by either an NMDA receptor antagonist (MK-801) or AMPA receptor antagonist (DNQX), thus suggesting that NMDA-induced pSLA was mediated by NMDA and non-NMDA receptors. The present results provide pharmacologic evidence of a functional inhibitory action of topiramate on glutamate receptor activity in invertebrates and provide a sensitive, quantifiable end-point for studying anti-seizure pharmacology.[1]

References

Topiramate antagonizes NMDA- and AMPA-induced seizure-like activity in planarians. Rawls, S.M., Thomas, T., Adeola, M., Patil, T., Raymondi, N., Poles, A., Loo, M., Raffa, R.B. Pharmacol. Biochem. Behav. (2009) [Pubmed]

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