Abstract
Background: In previous works, alterations of neurotransmitters and neuropeptides in the brain areas
involved in generalized epilepsy have been reported.
Objective: We reviewed the alterations of these neurotransmitters and neuropeptides in the following brain areas
involved in generalized epilepsy: hippocampus, hypothalamus, thalamus and cerebral cortex. In these brain areas,
the neural networks are also actualized. The mechanisms of action of newer antiepileptic drugs in the treatment of
generalized epilepsy are also discussed.
Results: Up-dating the neurotransmitter and neuropeptide alterations, we found that hippocampal GABAergic
neurons presynaptically inhibit epileptogenic neurons via GABAB receptors. Epilepsy modulating neuropeptides
(galanin, neuropeptide Y, dynorphin) are also involved. GABA deficiency, serotonin hyperactivity, dopamine
hyperactivity and glutamate excitotoxicity can enhance ictogenesis: neurons containing these neurotransmitters
form the main neural circuit. An increased excitability occurs when the alteration of these neurotransmitters is
permanent.
Conclusion: In preclinical studies, the GABAB receptor agonist GS 39,783 exerted a good antiepileptic effect.
Perampanel, an AMPA receptor antagonist, showed good clinical effects in the treatment of partial-onset seizures
and primary generalized tonic-clonic seizures. In this treatment, perampanel can be combined with other antiepileptic
drugs. Brivaracetam, which shows a high affinity for the synaptic vesicle 2A, exerted a good efficacy in the
treatment of adult focal seizures and secondarily generalized tonic-clonic seizures.
Keywords:
Antiepileptic drug, brivaracetam, dopamine, GABAB receptor agonist, generalized epilepsy, glutamate, neurotransmitter imbalance,
perampanel.
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