Effects of carbamazepine, phenytoin, valproic acid, oxcarbazepine, lamotrigine, topiramate and vinpocetine on the presynaptic Ca2+ channel-mediated release of [3H]glutamate: comparison with the Na+ channel-mediated release.

The effect of carbamazepine, phenytoin, valproate, oxcarbazepine, lamotrigine and topiramate, that are among the most widely used antiepileptic drugs (AEDs), and of the new putative AED vinpocetine on the Ca(2+) channel-mediated release of [(3)H]Glu evoked by high K(+) in hippocampal isolated nerve endings was investigated. Results show that carbamazepine, oxcarbazepine and phenytoin reduced [(3)H]Glu release to high K(+) to about 30% and 55% at concentrations of 500 microM and 1500 microM, respectively; lamotrigine and topiramate to about 27% at 1500 microM; while valproate failed to modify it. Vinpocetine was the most potent and effective; 50 microM vinpocetine practically abolished the high K(+) evoked release of [(3)H]Glu. Comparison of the inhibition exerted by the AEDs on [(3)H]Glu release evoked by high K(+) with the inhibition exerted by the AEDs on [(3)H]Glu release evoked by the Na(+) channel opener, veratridine, shows that all the AEDs are in general more effective blockers of the presynaptic Na(+) than of the presynaptic Ca(2+) channel-mediated response. The high doses of AEDs required to control seizures are frequently accompanied by adverse secondary effects. Therefore, the higher potency and efficacy of vinpocetine to reduce the permeability of presynaptic ionic channels controlling the release of the most important excitatory neurotransmitter in the brain must be advantageous in the treatment of epilepsy.

Effects of carbamazepine, phenytoin, lamotrigine, oxcarbazepine, topiramate and vinpocetine on Na+ channel-mediated release of [3H]glutamate in hippocampal nerve endings.

Several of the most effective antiepileptic drugs are believed to stop the paroxysmal neuronal activity acting as Na(+) channel blockers. However, no single study comparing in parallel the potency and efficacy of the most commonly used antiepileptic drugs on brain Na(+) channel-mediated responses is available. In the present study the effects of increasing concentrations of carbamazepine, phenytoin, lamotrigine, oxcarbazepine and topiramate, which are among the most frequently used antiepileptic drugs, and of the new putative antiepileptic drug, vinpocetine, on the release of glutamate (Glu) elicited by the Na(+) channel opener, veratridine were investigated in hippocampal isolated nerve endings preloaded with the labeled excitatory amino acid neurotransmitter. The present results show that carbamazepine, phenytoin, lamotrigine and oxcarbazepine, in the range from 150 to 1500 microM, progressively inhibit [(3)H]Glu release induced by veratridine. Also vinpocetine progressively inhibits the veratridine-induced response, but in a much lower range of concentrations (from 1.5 to 15 microM), whereas topiramate only exerts a modest inhibition (20%) of Glu release to veratridine at the highest dose tested (1500 microM). These results indicate that the mechanism of action of several of the most widely used antiepileptic drugs involves reduction in cerebral presynaptic voltage sensitive Na(+) channels permeability. Considering that the high doses of antiepileptic drugs required to control seizures are frequently accompanied by adverse secondary effects, the higher potency of vinpocetine to reduce Na(+) channels permeability might be advantageous.

Efecto potenciador de la amitriptilina sobre los analgésicos en pacientes con dolor oncológico / Potenciator effect of amitriptyline on the analgesics in patients with oncological pain

Se evaluó la eficacia e un antidepresivo tricíclico (amitriptilina) como potenciador de analgésicos en pacientes oncológico terminales, con dolor resistente a tratamiento convencional. El estudio se realizó con un diseño doble ciego, controlado con placebo. El efecto del medicamento se determinó mediante tres índices: el dolor al momento de la entrevista, el dolor habitual y el peor dolor durante la última semana, que se calificaron numéricamente. Se definió como mejoría la reducción en por lo menos el 25% del dolor manifestado al inicio del tratamiento. Unicamente en el grupo recibiendo amitriptilina se observaron mejorías del 100%, aunque las diferencias entre ambos grupos no fueron significativas. Se comentan los resultados y los problemas en la realización de este tipo de estudios