The single and combined effects of carbamazepine and vinpocetine on the release of the excitatory amino acid neurotransmitter glutamate, on the rise in internal Na+ (Na-i, as determined with SBFI), and on the rise in internal Ca2+ (Ca-i, as determined with fura-2) induced by an increased permeability of presynaptic Na+ channels, with veratridine, or by an increased permeability of presynaptic Ca2+ channels with high K+, were investigated in isolated hippocampal nerve endings. The present study shows that carbamazepine and vinpocetine, both inhibit dose dependently the release of preloaded [H-3]Glu induced by veratridine. However, carbamazepine is two orders of magnitude less potent than vinpocetine. The calculated IC50's for carbamazepine and vinpocetine to inhibit veratridine-induced [H-3]Glu release are 200 and 2 mu M, respectively. Consistently 150 mu M carbamazepine and 1.5 mu M vinpocetine reduce the veratridine-induced rise in Na-i in a similar extent. The single effects of carbamazepine and of vinpocetine on the presynaptic Na+ channel mediated responses, namely the rise in Nai and the release of Glu induced by veratridine, are additive. Responses that depend on the entrance of external Ca2+ via presynaptic Ca2+ channels, such as the release of [H-3]Glu and the rise in Ca-i induced by high K+, are insensitive to 300 mu M carbamazepine and slightly reduced by 5 mu M vinpocetine. It is concluded that the additive effects of carbamazepine, which is one of the most common antiepileptic drugs, and vinpocetine that besides its known neuroprotective action and antiepileptic potential is a memory enhancer, may perhaps be advantageous in the treatment of epileptic patients. (c) 2006 Published by Elsevier Ltd.
