Neuropharmacology of Antiseizure Drugs

Abstract

Background Antiseizure drugs (ASDs) are the primary therapy for epilepsy, with more than 20 drugs introduced into clinical practice to date. These drugs are typically grouped by their mechanisms of action and therapeutic spectrum. This article aims to educate non‐neurologists and medical students about the new frontiers in the pharmacology of ASDs and presents the current state of the literature on the efficacy and tolerability of these agents. Methods Randomized controlled trials, observational studies, and evidence‐based meta‐analyses of ASD efficacy and tolerability as initial monotherapy for epileptic seizures and syndromes were identified in PubMed, EMBASE, the Cochrane Library, and Elsevier Clinical Pharmacology. Results The choice of ASD varies primarily according to the seizure type. Practical guidelines for ASD selection in patients with new‐onset and drug‐resistant epilepsy were recently published. The guidelines have shown that the newer‐generation drugs, which have unique mechanistic and pharmacokinetic properties, are better tolerated but have similar efficacy compared with the older drugs. Several ASDs are effective as first‐line monotherapy in focal seizures, including lamotrigine, carbamazepine, phenytoin, levetiracetam, and zonisamide. Valproate remains the first‐line drug for many patients with generalized and unclassified epilepsies. However, valproate should be avoided, if possible, in women of childbearing potential because of teratogenicity. Toxicity profile precludes several drugs from use as first‐line treatment, for example, vigabatrin, felbamate, and rufinamide. Conclusions Antiseizure drugs have different pharmacologic profiles that should be considered when selecting and prescribing these agents for epilepsy. These include pharmacokinetic properties, propensity for drug‐drug interactions, and adverse effects.

Clemizole and trazodone are effective antiseizure treatments in a zebrafish model of STXBP1 disorder

“…STXBP1‐related disorders are classified as a drug‐resistant epilepsy, eg, failure to achieve seizure control with at least two ASMs 31 . Using an electrophysiology LFP‐based assay, we tested five ASMs (PHT, VPA, ESX, LEV, and DZP) covering a wide mechanism of action spectrum 32,33 . Continuous LFP recordings (60 min) were obtained from agarose‐immobilized stxbp1b mutant larvae.…”

Recent Developments in Autism Genetic Research: A Scientometric Review from 2018 to 2022

“…The smallest cluster—namely, Cluster #14 “Antiseizure Drug”—has the paper authored by Hakami [ 208 ] as major citing document, with a coverage of 4 and a GCS of 2. The naming of this cluster is based on a series of two papers written by Hakami [ 208 , 209 ] on antiseizure drugs, and may be related to ASD due to the higher prevalence of seizure and epilepsy diagnoses among these individuals [ 210 ]. Similarly, other contributing papers focused on understanding the genetic bases of epilepsy [ 211 , 212 , 213 ] and epilepsy treatment [ 214 , 215 ].…”

Preclinical evaluation of drug treatment options for sleep‐related epileptiform spiking in Alzheimer's disease

“…On the other hand, the main mechanism of action of LTG is considered blockade of voltage‐gated sodium channels as of many other anti‐seizure drugs. 24 Interestingly, LTG was found to worsen seizures in the rare severe myoclonic epilepsy, aka Dravet syndrome, 25 which is caused by a mutation in the SCN1A gene coding for the α‐subunit of the Nav1.1 channel that is mainly responsible for action potential generation. 26 Nav1.1 closely relates to basic Aβ pathology in that its β‐subunit is a substrate to BACE1.…”