Abstract
Aim of this study was to learn whether the antiepileptic drugs (AEDs) carbamazepine, lamotrigine, phenytoin, gabapentin, pregabalin, levetiracetam, and valproate (all at 100 μM) presynaptically influence the neurotransmission of the excitatory transmitter glutamate. The effects of these frequently used AEDs were examined on 3H-glutamate release from superfused synaptosomes of both rat and human neocortex. Release was evoked by elevation of buffer [K+] from 3 to 15 mM or by the Na+ channel activator veratridine (1, 3.2, and 10 μM). Buffer [K+] elevation induced 3H-glutamate exocytosis, which was Ca2+-, but not Na+-, dependent and which was accompanied only in human tissue by release through transporter reversal. In rat tissue, release was diminished by the Na+ channel inhibitors carbamazepine, lamotrigine, and phenytoin, which therefore may also affect presynaptic Ca2+ channels. Interestingly, levetiracetam increased 3H-glutamate release. In contrast, the tested AEDs did not affect K+-evoked 3H-glutamate release in human tissue, neither when the transporters were operative nor when exocytosis was isolated by transporter blockade. Veratridine-evoked 3H-glutamate release was a Na+-dependent transmitter efflux through reversed transporters in both species which in human synaptosomes was accompanied by exocytosis. The latter depended on external Ca2+. Carbamazepine, lamotrigine, and phenytoin reduced this release from both rat and human tissue. There is an obvious species difference in the effects of carbamazepine, lamotrigine, and phenytoin on K+-evoked 3H-glutamate release while their inhibitory effects on veratridine-evoked release were similar. Thus, the depression of 3H-glutamate release by carbamazepine, lamotrigine, and phenytoin may be due to inhibited synaptosomal Na+ or Ca2+ influx.
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Kammerer, M., Brawek, B., Freiman, T.M. et al. Effects of antiepileptic drugs on glutamate release from rat and human neocortical synaptosomes. Naunyn-Schmiedeberg's Arch Pharmacol 383, 531–542 (2011). https://doi.org/10.1007/s00210-011-0620-3
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DOI: https://doi.org/10.1007/s00210-011-0620-3