Neurotransmission in Epilepsy

Abstract

Summary: Some evidence indicates that in some types of focal epilepsy the enhanced excitability is due in part to impaired γ‐aminobutyric acid (GABA)ergic inhibitory feedback. One form that this can take is impaired excitatory input to GABAergic interneurons. Enhanced excitatory receptor sensitivity, most characteristically involving N‐methyl‐D‐aspartate (NMDA) receptors, has been identified in kindled rodents and in focal epilepsy in humans. Drugs that enhance GABA‐mediated inhibition are anticonvulsant in many syndromes of generalized and focal epilepsy. Mechanisms through which this occurs include direct interaction with the GABAhenzodiazepine (BZD) receptor (BZDs, barbiturates, chlormethiazole), inhibition of GABA‐transaminase (vigabatrin, VGB) and blocking GABA uptake (tiagabine, TGB). Glutamate receptor antagonists (both NMDA and non‐NMDA antagonists) are potent anticonvulsants in many animal models of epilepsy. Whether pure glutamate receptor antagonists will have a clinical role as antiepileptic drugs (AEDs) remains to be established.

Antiepileptic Effects of Tiagabine, a Selective GABA Uptake Inhibitor, in the Rat Kindling Model of Temporal Lobe Epilepsy

“…A variety of clinical and experimental findings have suggested that functional impairment of the GABAergic systems plays a fundamental role in the etiology of epilepsy (21,22). Recent clinical studies conducted in patients with TLE demonstrated impairment of increase in extracellular GABA concentration in the epileptogenic HIPP during seizures (23).…”

Histamine H3 receptor as a potential target for cognitive symptoms in neuropsychiatric diseases

“…Notably, CEP-26401 completed phase 1 of a clinical study addressing its pharmacokinetics and pharmacodynamics in healthy subjects for cognition and sleep-wake indications without disclosing the clinical outcomes of these studies (ClinicalTrials.gov trial registration number: NCT01903824) (Figure 10, Table 1&4). Of specific interest is pitolisant (also known as triprolisant) [30,[102][103][104] [30,[133][134][135] which is a potent H3R antagonist (Figure 10, Table 1) [102,[105][106][107]. Preclinically, pitolisant was shown to enhance dopamine and acetylcholine levels in microdialysates of the prefrontal cortex in rats [102].…”

Anxiolytic and anticonvulsive activity of Sesbania grandiflora leaves in experimental animals

“…Both BE and diazepam prevented the occurrence of lithium-pilocarpine induced seizures (Sherman, 1991). Since epilepsy is linked to low GABA levels in the brain (Meldrum, 1995), the effect of the BE on the brain content of GABA was investigated. An increase in the GABA content of the brain was observed and this could be the likely mechanism of anticonvulsant action of BE, as drugs increasing GABAergic transmission inhibit seizures (Gupta and Malhotra, 1997;Rang et al, 1999).…”