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Epilepsy and Neurotransmitters Basis for a New Pharmacological Approach to Antiepileptic Therapy

  • Giuliano Avanzini
  • Silvana Franceschetti
Part of the Ettore Majorana International Science Series book series (EMISS, volume 7)

Summary

Impairment of inhibitory synaptic mechanisms plays an important role in epileptogenesis. Epileptiform activity can be elicited by drugs that decrease GABA-mediated inhibition (such as bicuculline and penicillin) and can be suppressed by topical application of GABA. The effectiveness of some widely used antiepileptic drugs such as sodium valproate, benzodiazepines and barbiturates has been related to their GABA-ergic activity. Sodium valproate increases brain GABA content by inhibiting its metabolic conversion to succinate. Benzodiazepines bind to specific membrane receptors and displace an endogenous protein which inhibits GABA activity. These observations have improved the understanding of basic epileptogenic mechanisms and have promoted the development of new antiepileptic drugs. The anticonvulsant effects in experimental models and in man of some new compounds that inhibit GABA-transaminase (γ-acetylenic GABA and γ-vinyl GABA) or act as GABA-receptors agonists (LS-76002) look particularly promising. Brain monoamines have also been implicated in the pathophysiology of epilepsy. Chemical or mechanical lesions of serotonin-containing raphe neurons have been reported to enhance the occurrence and magnitude of seizures induced by different experimental procedures, while electrical stimulation of raphe nuclei significantly increases the threshold for seizures induced by amigdaloid kindling. These effects might be related to the inhibition exerted by ascending and descending serotonergic pathways on their targets. However, a comprehensive review of experimental and clinical studies failed to show a well-defined relationship between serotonin and epilepsy. At present the serotonergic system seems to be implicated only in very special cases of epileptiform phenomena (e.g. myoclonus), in which serotonin precursors have shown a beneficial effect in both experimental models and humans.

Keywords

Sodium Valproate aUdiogenic Seizure Succinic Semialdehyde Human Epilepsy Nipecotic Acid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Giuliano Avanzini
    • 1
  • Silvana Franceschetti
    • 1
  1. 1.Department of NeurophysiologyIstituto Neurologico C. BestaMilanItaly

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