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Lamotrigine and Carbamazepine Affect Differently the Release of D-[3H]Aspartate from Mouse Cerebral Cortex Slices: Involvement of NO

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Abstract

The effects of lamotrigine and carbamazepine on the release of preloaded D-[3H]aspartate and the involvement of nitric oxide were studied with mouse cerebral cortical slices in a superfusion system. Lamotrigine inhibited the veratridine-evoked release, whereas the K+-stimulated release was attenuated more strongly by carbamazepine than by lamotrigine. These effects were accentuated by the N-methyl-D-aspartate receptor antagonist L-2-amino-5-phosphonovalerate and the nitric oxide synthase inhibitor L-nitroarginine, but diminished by the nitric oxide donor sodium nitroprusside. The results show that in addition to the blockade of voltage-sensitive Na+ (and Ca2+) channels, NO-mediated mechanisms are probably involved in the anticonvulsant actions of carbamazepine and, in particular, those of lamotrigine.

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REFERENCES

  1. Rogawski, M. E., and Porter, R. J. 1990. Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacol. Rev. 42:223-286.

    PubMed  Google Scholar 

  2. Macdonald, R. L., and Kelly, K. M. 1994. Mechanisms of action of currently prescribed and newly developed antiepileptic drugs. Epilepsia 35:Suppl. 4, S41-S50.

    Google Scholar 

  3. Stefani, A., Spadoni, F., Siniscalchi, A., and Bernardi, G. 1996. Lamotrigine inhibits Ca2+ currents in cortical neurons: functional implications. Eur. J. Pharmacol. 307:113-116.

    PubMed  Google Scholar 

  4. Wang, S.-J., Huang, C.-C., Hsu, K.-S., Tsai, J.-J., and Gean, P.-W. 1996. Inhibition of N-type calcium currents by lamotrigine in rat amygdalar neurones. Neuroreport 7:3037-3040.

    PubMed  Google Scholar 

  5. Yoshimura, R., Yanagihara, N., Terao, T., Minami, K., Abe, K., and Izumi, F. 1995. Inhibition by carbamazepine of various ion channels-mediated catecholamine secretion in cultured bovine adrenal medullary cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 352:297-303.

    Google Scholar 

  6. Waldmeier, P. C., Martin, P., Stöcklin, K., Portet, C., and Schmutz, M. 1996. Effect of carbamazepine, oxcarbamazepine and lamotrigine on the increase in extracellular glutamate elicited by veratridine in rat cortex and striatum. Naunyn-Schmiedeberg's Arch. Pharmacol. 354:164-172.

    Google Scholar 

  7. Lizasoian, I., Knowles, R. G., and Moncada, S. 1995. Inhibition by lamotriginine of the generation of nitric oxide in rat forebrain slices. J. Neurochem. 64:636-642.

    PubMed  Google Scholar 

  8. Moncada, S., Palmer, R. M. J., and Higgs, E. A. 1989. Biosyn-thesis of nitric oxide from L-arginine. A pathway for the regulation of cell function and communication. Biochem. Pharmacol. 38:1709-1715.

    PubMed  Google Scholar 

  9. Moncada, S., Palmer, R. M. J., and Higgs, E. A. 1991. Nitric oxide: physiology, pathophysiology and pharmacology. Pharmacol. Rev. 43:109-142.

    PubMed  Google Scholar 

  10. Garthwaite, G., Charles, S. L., and Chess-Williams, R. 1988. Endothelium-derived relaxing factor release on activation of NMDA receptor suggests a role as intercellular messenger in the brain. Nature 336:385-388.

    PubMed  Google Scholar 

  11. Bredt, D. S., and Snyder, S. H. 1990. Isolation of nitric oxide synthase, a calmodulin-requiring enzyme. Proc. Natl Acad. Sci. USA 87:682-685.

    PubMed  Google Scholar 

  12. Shibuki, K., and Okada, D. 1991. Endogenous nitric oxide release required for long-term synaptic depression in the cerebellum. Nature 349:326-328.

    Article  PubMed  Google Scholar 

  13. Ohkuma, S., Katsura, M., Guo, J.-L., Narihara, H., Hasegava, T., and Kuriyama, K. 1996. Role of peroxynitrite in [3H]γ-aminobutyric acid release evoked by nitric oxide and its mechanism. Eur. J. Pharmacol. 301:179-188.

    PubMed  Google Scholar 

  14. Przegalinski, E., Baran, L., and Siwanowicz, J. 1996. The role of nitric oxide in chemically-and electrically-induced seizures in mice. Neurosic. Lett. 217:145-148.

    Google Scholar 

  15. Lipton, S. A., Chol, Y.-B., Pan, Z.-H., Lei, S. Z., Chen, H.-S. V., Sucher, N. J., Loscalzo, J., Singel, D. J., and Stamler, J. S. 1993. A redox-based mechanism for the neuroprotective and neurode-structive effects of nitric oxide and related nitrosocompounds. Nature 364:626-632.

    Article  PubMed  Google Scholar 

  16. Segieth, J., Getting, S. J., Biggs, C. S., and Whitton, P. S. 1995. Nitric oxide regulates excitatory amino acid release in a biphasic manner in freely moving rats. Neurosci. Lett. 200:101-104.

    PubMed  Google Scholar 

  17. Kontro, P., and Oja, S. S. 1987. Taurine and GABA release from mouse cerebral cortex slices: potassium stimulation releases more taurine than GABA from developing brain. Dev. Brain Res. 37:277-291.

    Google Scholar 

  18. Drejer, J., Larsson, O. M., and Schousboe, A. 1983. Characterization of uptake and release processes for D-and L-aspartate in primary cultures of astrocytes and cerebellar granule cells. Neurochem. Res. 8:231-243.

    PubMed  Google Scholar 

  19. Wheeler, D. D. 1984. Kinetics of D-aspartic acid release from rat cortical synaptosomes. Neurochem. Res. 15:889-898.

    Google Scholar 

  20. Waldmeier, P. C., Baumann, P. A., Wicki, P., Feldtrauer, J.-J., and Schmutz, M. 1995. Similar potency of carbamazepine, oxcarbamazepine and lamotrigine in inhibiting the release of glutamate and other neurotransmitters. Neurology 45:1907-1913.

    PubMed  Google Scholar 

  21. Leach, M. J., Marden, C. M., and Miller, A. A. 1986. Pharmacological studies on lamotrigine, a novel potential antiepileptic drug: II. Neurochemical studies on the mechanisms of action. Epilepsia 27:490-497.

    PubMed  Google Scholar 

  22. Saransaari, P., and Oja, S. S. 1992. Release of D-aspartate from cerebral cortex slices from developing and adult mice. Mol. Neuropharmacol. 2:189-191.

    Google Scholar 

  23. Saransaari, P., and Oja, S. S, 1997. Kainate potentiates D-aspartate release from hippocampal slices from developing and ageing mice. Proc. West. Phamacol. Soc. 40:29-32.

    Google Scholar 

  24. Ulbricht, W. 1969. The effect of veratridine on excitable membranes of nerve and muscle. Ergebn. Physiol. 61:18-71.

    PubMed  Google Scholar 

  25. Bridges, R. J., Stanley, M. S., Anderson, M. W., Cotman, C. W., and Chamberlin, A. R. 1991. Conformationally defined neurotransmitter analogues. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer. J. Med. Chem. 34:717-725.

    PubMed  Google Scholar 

  26. Zuiderwijk, M., Veenstra, E., Lopes da Silva, F. H., and Ghijsen, W. E. J. M. 1996. Effects of uptake carrier blockers SK & F 89976-A and L-trans-PDC on in vivo release of amino acids in rat hippocampus. Eur. J. Pharmacol. 307:275-282.

    PubMed  Google Scholar 

  27. Saransaari, P., and Oja, S. S. 1994. Regulation of D-aspartate release by glutamate and GABA receptors in cerebral cortical slices from developing and ageing mice. Neuroscience 60:191-198.

    PubMed  Google Scholar 

  28. Garthwaite, J. 1991. Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci. 14:60-67.

    Article  PubMed  Google Scholar 

  29. Schuman, E. R., and Madison, D. V. 1994. Nitric oxide and synaptic function. Annu. Rev. Neurosci. 17:153-183.

    PubMed  Google Scholar 

  30. East, S. J., and Garthwaite, J. 1991. NMDA receptor activation in rat hippocampus induces cyclic GMP formation through the L-arginine-nitric oxide pathway. Neurosci. Lett. 123:17-19.

    PubMed  Google Scholar 

  31. Hoyt, K. R., Tang, L.-H., Aizenman, E., and Reynolds, I. J. 1992. Nitric oxide modulates NMDA-induced increases in intracellular Ca2+ in cultured rat forebrain neurons. Brain Res. 592:310-316.

    PubMed  Google Scholar 

  32. Knowles, R. G., and Moncada, S. 1994. Nitric oxide synthases in mammals. Biochem. J. 298:249-258.

    PubMed  Google Scholar 

  33. Lei, S.-Z., Pan, Z.-H., Aggarwal, S. K., Chen, H.-S. V., Hartman, J., Sucher, N. J., and Lipton, S. A. 1992. Effect of nitric oxide production on the redox modulatory site of the NMDA receptor-channel complex. Neuron 8:1087-1099.

    PubMed  Google Scholar 

  34. Manzoni, O., Prezeau, L., Marin, P., Deshager, S., Bockaert, J., and Fagni, L. 1992. Nitric oxide-induced blockade of NMDA receptors. Neuron 8:653-662.

    Article  PubMed  Google Scholar 

  35. Kamisaki, Y., Maeda, K., Ishimura, M., Omura, H., Moriwaki, Y., and Itoh, T. 1994. No enhancement by nitric oxide of glutamate release from P2 and P3 synaptosomes of rat hippocampus. Brain Res. 644:128-134.

    PubMed  Google Scholar 

  36. Kamisaki, Y., Wada, K., Nakamoto, K., and Itoh, T. 1995. Nitric oxide inhibition of the depolarization-evoked glutamate release from synaptosomes of rat cerebellum. Neurosci. Lett. 194:5-8.

    PubMed  Google Scholar 

  37. Klatt, P., Schmidt, K., Brunner, F., and Mayer, B. 1994. Inhibitors of brain nitric oxide synthase: binding kinetics, metabolism, and enzyme inactivation. J. Biol. Chem. 269:1674-1680.

    PubMed  Google Scholar 

  38. Zhu, X.-Z., and Luo, L.-G. 1992. Effect of nitroprusside (nitric oxide) on endogenous dopamine release from rat striatal slices. J. Neurochem. 59:932-935.

    PubMed  Google Scholar 

  39. Chen, D.-Z., Ohkuma, S., and Kuriyama, K. 1996. Characteristics of nitric oxide-evoked [3H]taurine release from cerebral cortical neurons. Neurochem. Int. 28:601-607.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, Russian Academy of Medical Sciences, Baltiskaya Street 8, 125315, Moscow, Russia

    Ilya Afanas'ev, Vladimir Kudrin & Kirill S. Rayevsky

  2. Tampere Brain Research Center, University of Tampere Medical School, Box 607, FIN-33101, Tampere, Finland

    Ilya Afanas'ev, Vladimir Kudrin, Vince Varga, Pirjo Saransaari & Simo S. Oja

  3. Department of Animal Physiology, Kossuth Lajos University of Sciences, Box 18, H-4010, Debrecen, Hungary

    Vince Varga

  4. Department of Clinical Physiology, Tampere University Hospital, Box 2000, FIN-33521, Tampere, Finland

    Simo S. Oja

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Afanas'ev, I., Kudrin, V., Rayevsky, K.S. et al. Lamotrigine and Carbamazepine Affect Differently the Release of D-[3H]Aspartate from Mouse Cerebral Cortex Slices: Involvement of NO. Neurochem Res 24, 1153–1159 (1999). https://doi.org/10.1023/A:1020716621300

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