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.

Sertraline inhibits pre‐synaptic Na+ channel‐mediated responses in hippocampus‐isolated nerve endings

“…Incubation was stopped by centrifugation. The supernatants containing the released neurotransmitters and the pellets containing the neurotransmitters inside nerve endings were treated as described previously (Sitges et al. 2009).…”

“…Incubation was stopped by centrifugation. The supernatants containing the released neurotransmitters and the pellets containing the neurotransmitters inside nerve endings were treated as described previously (Sitges et al 2009). The neurotransmitter concentrations in the samples injected to the HPLC system were standardized per mg of synaptosomal protein.…”

Mechanisms underlying striatal vulnerability to 3‐nitropropionic acid

“…To investigate the changes exerted by different drugs on DA metabolism, in previous studies we used an experimental design that allowed us to measure their effects on the concentrations of neurotransmitters and some of their metabolites, including DA and DOPAC, inside and outside cerebral isolated nerve endings (Sitges et al. 2000, 2009; Trejo et al.…”

Effects of Vinpocetine on Random Skin Flap Survival in Rats

“…In addition, vinpocetine has been proven to selectively inhibit voltage-sensitive sodium (Na þ ) channels, causing a dose-dependent decrease in evoked extracellular calcium (Ca 2þ ) ions, which will be responsible for the cell damage induced by ischemia/reperfusion and cytotoxic edema. 17,18 Those mechanisms discussed above may explain the present experimental result: tissue edema and inflammatory infiltration in Group 1 were lower that those seen in Group 2.…”