Classical Neurotransmitters and Neuropeptides Involved in Generalized Epilepsy: A Focus on Antiepileptic Drugs

F.-M.      Werner; R.      Covenas

Abstract

We describe the alterations of classical neurotransmitters and neuropeptides in generalized epilepsy. A neuronal network in this disease is developed. Gamma aminobutyric acid (GABA) hypoactivity induces dopamine hyperactivity because dopaminergic neurons are affected by the inhibitory influence of the GABAergic system through GABAA receptors. Glutamate hyperactivity is exerted via presynaptic N-methyl-D-aspartate (NMDA) receptors, which strongly inhibit serotoninergic neurons, and via postsynaptic ionotropic glutaminergic receptors, which can induce epileptic seizures. A collection of specific subreceptors of classical neurotransmitters and neuropeptides involved in epileptogenesis is reported. The question arises whether agonists/antagonists of neuropeptides (neuropeptide Y, galanin…) could have additional antiepileptic properties. The effect of conventional and newer antiepileptic drugs interfering with these subreceptors is discussed on the basis of the neuronal network suggested. From these data, it is concluded that new antiepileptic drugs interfering with other specific subreceptors (GABAB antagonists, metabotropic glutaminergic receptors subtype 5 (mGlu5R) antagonists, mGlu2/3R agonists, 5-serotonin (5-HT7) agonists) could further stabilize the neuronal network in generalized epilepsy.

Keywords: GABA, glutamate, serotonin, dopamine, acetylcholine, adenosine, neuropeptide Y, galanin, antiepileptic drugs, generalized epilepsy