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April 29, 2023

+ + + + 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 several publications [5, 11, 29, 62, 63, 168, 169] and 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) for the duration of 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 example PTZ. The best-characterized and predictive model is amygdala PKCθ MedChemExpress kindling [29]. Importantly, testing of novel compounds within the kindling model was much more predictive of clinical efficacy than testing inside the MES test, as as an example demonstrated by vigabatrin, levetiracetam, and tiagabine (Table 1). The finding of L cher and H ack [32] that levetiracetam is specifically helpful in the amygdalakindling model was critical in the additional improvement of this compound, which can be now one of the most extensively utilized ASMs [33]. As shown in Table 1, ASMs differ markedly in their efficacy in animal models. ASMs is usually grouped into three categories: (1) ASMs using a narrow spectrum of efficacy which include ethosuximide (only active against absence seizures) or vigabatrin (active in the kindling model but not the other models shown in Table 1); (2) ASMs that mainly act in MES and focal-onset seizure models (the vast majority of compounds shown in Table 1), and (three) ASMs using a broad spectrum of efficacy for instance the benzodiazepines, brivaracetam, topiramate, valproate, and alkyl-carbamates for instance cenobamate. No less than in element, the preclinical spectrum of antiseizure efficacies resembles the clinical spectrum (Table 1). For example, ethosuximide is only powerful in the GAERS model and practically exclusively employed for the therapy of absence seizures in humans; phenytoin and carbamazepine act mostly against focal-onset and mostly generalized tonic-clonic seizures in animal models and individuals, and benzodiazepines and valproate exhibit a broad spectrum of preclinical and clinical efficacy. In addition to the preclinical models illustrated in Table 1, distinct animal models for pediatric genetic epilepsies, like P2Y14 Receptor Gene ID Lennox astaut syndrome, infantile spasms (West syndrome), Dravet syndrome, and TSC is usually made use of to learn novel ASMs for the difficult-to-treat seizures in these syndromes [34]. As described, several ASMs, like cannabidiol, rufinamide, stiripentol, everolim