Characterization of phenytoin, carbamazepine, vinpocetine and clorgyline simultaneous effects on sodium channels and catecholamine metabolism in rat striatal nerve endings.
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.
Sitges
María
M
Depto. de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Apartado Postal 70228, Ciudad Universitaria, 04510 Mexico, D.F., Mexico. sitges@biomedicas.unam.mx
Aldana
Blanca I
BI
Chiu
Luz M
LM
Nekrassov
Vladimir
V
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects / Q000494:pharmacology*; D001224:Aspartic Acid / Q000378:metabolism; D002220:Carbamazepine / Q000009:adverse effects / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D003010:Clorgyline / Q000009:adverse effects / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D004298:Dopamine / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D010672:Phenytoin / Q000009:adverse effects / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D062687:Sodium Channel Agonists; D015222:Sodium Channels / Q000378:metabolism*; D014748:Vinca Alkaloids / Q000009:adverse effects / Q000494:pharmacology
D000927:Anticonvulsants; D002395:Catecholamines; D008996:Monoamine Oxidase Inhibitors; D062687:Sodium Channel Agonists; D015222:Sodium Channels; D014748:Vinca Alkaloids; D005973:Glutamine; D015102:3,4-Dihydroxyphenylacetic Acid; D001224:Aspartic Acid; D002220:Carbamazepine; C013983:vinpocetine; D010672:Phenytoin; D003010:Clorgyline; D004298:Dopamine