+ + + + 0 + 0 + + + + + + + + + 0 + 0 + + + + + 0 + + 0 + + 0 + 0 + 0 + 0 + + + 0 + 0 + + + + + + 0 + + + 0 + + + + + + 0 + + + + + Absence seizures (GAERS or WAG/Rij rat strains) Focal-onset seizures Dravet syndrome + 0 + + + + 0 0 + 0 + + 0 0 0 + 0 + + 0 + Focal seizures (6-Hz test; 32 or 44 mA) + + + + + + + 0 + + + + 0 + + + + + + + + 0 + +DrugEfficacy in preclinical rodent modelsPrimary generalized tonic-clonic seizures (MES test)Acetazolamidea+Brivaracetam+Cannabidiol+Carbamazepine+Cenobamate+Clobazam+Clonazepama+Eslicarbazepine acetate+EthosuximideFelbamate+Fenfluramine+Gabapentin+Lacosamide+Lamotrigine+LevetiracetamOxcarbazepine+Perampanel+Phenobarbital+Phenytoin+Pregabalin+Primidone+Retigabine (ezogabine)b +Rufinamide+Stiripentol+Sulthiamec+TiagabineTopiramate+Valproate+VigabatrinZonisamide+Data sourced from different publications [5, 11, 29, 62, 63, 168, 169] in addition to a PubMed search of recent literatureGAERS genetic absence epilepsy rat from Strasbourg, Hz Herz, MES maximal electroshock seizures, WAG/Rij Wistar Albino Glaxo from Rijswijk, + indicates efficacy, 0 indicates inefficacy or worsening of seizures, + indicates inconsistent or preliminary findings, indicates insufficient dataabLoss of efficacy (tolerance) through chronic administrationW. L cher, P. KleincWithdrawn inUsed in Europe in self-limited childhood (rolandic) epilepsy with centrotemporal spikesAntiseizure Medicationsamygdala, by transcorneal application of electrical stimuli, or by convulsants for instance PTZ. The best-characterized and predictive model is amygdala kindling [29]. Importantly, testing of novel compounds within the kindling model was a lot more predictive of clinical efficacy than testing inside the MES test, as for example demonstrated by vigabatrin, levetiracetam, and PKCĪ± Purity & Documentation tiagabine (Table 1). The locating of L cher and H ack [32] that levetiracetam is specifically helpful in the amygdalakindling model was vital in the further improvement of this compound, which can be now among essentially the most widely employed ASMs [33]. As shown in Table 1, ASMs differ markedly in their efficacy in animal models. ASMs may be grouped into three categories: (1) ASMs using a narrow spectrum of efficacy like ethosuximide (only active against absence seizures) or vigabatrin (active within the kindling model but not the other MMP-13 supplier models shown in Table 1); (2) ASMs that mostly act in MES and focal-onset seizure models (the vast majority of compounds shown in Table 1), and (three) ASMs with a broad spectrum of efficacy for example the benzodiazepines, brivaracetam, topiramate, valproate, and alkyl-carbamates such as cenobamate. No less than in portion, the preclinical spectrum of antiseizure efficacies resembles the clinical spectrum (Table 1). For instance, ethosuximide is only successful within the GAERS model and almost exclusively applied for the remedy of absence seizures in humans; phenytoin and carbamazepine act primarily against focal-onset and mainly generalized tonic-clonic seizures in animal models and sufferers, and benzodiazepines and valproate exhibit a broad spectrum of preclinical and clinical efficacy. As well as the preclinical models illustrated in Table 1, certain animal models for pediatric genetic epilepsies, which include Lennox astaut syndrome, infantile spasms (West syndrome), Dravet syndrome, and TSC can be utilized to discover novel ASMs for the difficult-to-treat seizures in these syndromes [34]. As described, many ASMs, like cannabidiol, rufinamide, stiripentol, everolim