Excitatory Amino Acids: Approaches to Rational Anticonvulsant Therapy
In recent years, enhancement of inhibitory transmission has come to be considered the most important rational approach to the design of novel anticonvulsant drugs (Meldrum, 1983). This has led to clinical trials involving several novel compounds, designed to enhance GABA-mediated inhibition such as Progabide and Vigabatrin. The alternative approach of seeking compounds that impair excitatory transmission has only recently attracted attention. It might be thought that impairing excitatory transmission is unlikely to suppress epileptic activity selectively while leaving normal function intact. However, as will be explained below, there are reasons why it may be possible to act selectively on the sustained abnormal discharge of epilepsy.
KeywordsAdenosine Diazepam Homocysteine Clonidine Salbutamol
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- Anderson, E., Baudry, M., Lynch, G. and Morris R.G.M. (in Press). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-Daspartate receptor antagonist, APV-5. Physiol. Soc.__, 38P.Google Scholar
- Chapman, A.G., Croucher, M.J. and Meldrum, B.S. (1984). Evaluation of anticonvulsant drugs in DBA/2 mice with sound-induced seizures. Arzneimitt. Forsch. 34., 1261–1264.Google Scholar
- Davies, J., Evans, R.H., Jones, A.W., Smith, D.A.S. and Watkins, J.C. (1982). Differential activation and blockade of excitatory amino acid receptors in the mammalian and amphibian central nervous system. Comp. Biochem. Physiol. 72C, 211–224.Google Scholar
- Dunwiddle, T.V. and Worth, T. (1982). Sedative and anticonvulsant effects of adenosine analogs in mouse and rat. J. Pharmacol, exp. Therap., 220, 70–76.Google Scholar
- MacDonald, R.L. (1983). Mechanisms of anticonvulsant drug action. In Recent Advances in Epilepsy. (eds. T.A. Pedley and B.S. Meldrum). Churchill Livingstone Edinburgh.Google Scholar
- Meldrum, B.S. (1978). Photosensitive epilepsy in Papio papio as a model for drug studies. In Contemporary Clinical Neurophysiology, Suppl. 34: Electroencephalography Clinical Neurophysiology, (eds. E.A. Cobb and H. van Duijn). Elsevier, Amsterdam.Google Scholar
- Meldrum, B.S. (1983). Pharmacological considerations in the search for new anticonvulsant drugs. In Recent Advances in Epilepsy. (eds. T.A. Pedley and B.S. Meldrum). Churchill Livingstone, London.Google Scholar
- Meldrum, B. and Braestrup, C. (1984). GABA and the Anticonvulsant Action of Benzodiazepines and Related Drugs. In Actions and Interactions of GABA and Benzodiazepines. (eds. N.G. Bowery). Raven Press, New York.Google Scholar
- Skerritt, J.H., Johnston, G.A.R. (1984). Modulation of excitant amino acid release by convulsant and anticonvulsant drugs. In Neurotransmitters, Seizures and Epilepsy II. (eds. R.G. Fariello). pp.215–226, Raven Press, New York.Google Scholar