title: Classical neurotransmitters and neuropeptides involved in generalized epilepsy in a multi-neurotransmitter system: How to improve the antiepileptic effect?
abstract: Here, we describe in generalized epilepsies the alterations of classical neurotransmitters and neuropeptides acting at specific subreceptors. In order to consider a network context rather than one based on focal substrates and in order to make the interaction between neurotransmitters and neuropeptides and their specific subreceptors comprehensible, neural networks in the hippocampus, thalamus, and cerebral cortex are described. In this disease, a neurotransmitter imbalance between dopaminergic and serotonergic neurons and between presynaptic GABAergic neurons (hypoactivity) and glutaminergic neurons (hyperactivity) occurs. Consequently, combined GABAAagonists and NMDA antagonists could furthermore stabilize the neural networks in a multimodal pharmacotherapy. The antiepileptic effect and the mechanisms of action of conventional and recently developed antiepileptic drugs are reviewed. The GASH:Sal animal model can contribute to examine the efficacy of antiepileptic drugs. The issues of whether the interaction of classical neurotransmitters with other subreceptors (5-HT7, metabotropic 5 glutaminergic, A2Aadenosine, and alpha nicotinic 7 cholinergic receptors) or whether the administration of agonists/antagonists of neuropeptides might improve the therapeutic effect of antiepileptic drugs should be addressed. This article is part of a Special Issue entitled "Genetic and Reflex Epilepsies, Audiogenic Seizures and Strains: From Experimental Models to the Clinic".
authors.affiliation: Höhere Berufsfachschule für Altenpflege und Ergotherapie der Euro Akademie Pößneck, Pößneck, Germany; Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), University of Salamanca, Salamanca, Spain. Electronic address: felixm-werner@versanet.de.
authors.forename: Felix-Martin
authors.initials: FM
authors.lastname: Werner
authors.affiliation: Institute of Neurosciences of Castilla y León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems (Lab. 14), University of Salamanca, Salamanca, Spain. Electronic address: covenas@usal.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Coveñas
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004829:Epilepsy, Generalized / Q000188:drug therapy* / Q000378:metabolism*; D059330:GABAergic Neurons / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000927:Anticonvulsants; D009479:Neuropeptides; D018377:Neurotransmitter Agents
keywords: Antiepileptic drugs; Dopamine; GABA; Generalized epilepsy; Glutamate; Neural network; Serotonin; Topiramate