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Characterization of Phenytoin, Carbamazepine, Vinpocetine and Clorgyline Simultaneous Effects on Sodium Channels and Catecholamine Metabolism in Rat Striatal Nerve Endings

Abstract

The effects of two classic antiepileptic drugs (carbamazepine and phenytoin), a potential antiepileptic (vinpocetine) and a monoamine-oxidase inhibitor (clorgyline) on the simultaneous changes (detected by HPLC) on Glu, Asp, dopamine and DOPAC inside and outside striatal isolated nerve endings were investigated. Under resting conditions phenytoin, carbamazepine and clorgyline increased dopamine release. Phenytoin and clorgyline increased internal dopamine and decreased DOPAC formation. Carbamazepine decreased internal dopamine and practically did not change DOPAC formation. Glu and Asp release was unchanged. Neurotransmitter release induced by the Na+ channel opener veratridine was reduced by all the antiepileptic drugs tested, except phenytoin which, like clorgyline, facilitated veratridine-induced dopamine release. We conclude that besides the antagonism exerted by carbamazepine, phenytoin and vinpocetine on excitatory neurotransmitters release triggered by Na+ channel activation, that might importantly contribute to their anticonvulsant action, they exert different actions on striatal dopamine distribution, that might explain their different side effect profiles.

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Acknowledgments

The authors thank Araceli Guarneros for her excellent technical assistance. This work was partially supported by grants 225008 from PAPIIT and D-48695 from SEP-CONACYT. Blanca I. Aldana García scholarship was also supported by grant 225008 from PAPIIT.

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Sitges, M., Aldana, B.I., Chiu, L.M. et al. Characterization of Phenytoin, Carbamazepine, Vinpocetine and Clorgyline Simultaneous Effects on Sodium Channels and Catecholamine Metabolism in Rat Striatal Nerve Endings. Neurochem Res 34, 470–479 (2009). https://doi.org/10.1007/s11064-008-9805-7

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  • DOI: https://doi.org/10.1007/s11064-008-9805-7

Keywords

  • Antiepileptic drugs
  • Monoamino-oxidase
  • Dopamine
  • DOPAC
  • Glutamate
  • Aspartate
  • Veratridine