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The marketed and nonmarketed ASM drug lists are based on Odi et al.[1] and includes bumetanide (see text for further details).[10] The other drug lists are based on the World Health Organization's Collaborating Center for Drug Statistics Methodology, and the numbers in brackets refer to drug classes as defined in this database.[6] Drug combinations, gases, local anesthetics, drugs not approved for use by the US Food and Drug Administration (except for nonmarketed ASMs), and those that do not necessarily have to cross the blood-brain barrier to exert their effects (e.g., antiemetics and antimigraine drugs) were excluded. Keywords: antiepileptic drugs; efficacy; molecular weight; physicochemical properties; topological polar surface area EN antiepileptic drugs efficacy molecular weight physicochemical properties topological polar surface area 311 319 9 02/08/23 20230201 NES 230201 Key Points We found differences between physicochemical properties of antiseizure medications with proven clinical efficacy and those of other CNS drugs. MARKETED ASMS ARE MORE POLAR THAN OTHER CNS DRUGS ASMs additionally differ from other CNS drugs by generally having more surface area over polar atoms, as indicated by the higher TPSA values of the marketed ASM group relative to the nonmarketed ASMs and other CNS drugs (Figure 1B, Table 2). [Extracted from the article]

Therapeutic monoclonal antibodies (mAbs) have emerged as the fastest growing drug class. As such, mAbs are increasingly being co‐prescribed with other drugs, including antiseizure medications (ASMs). Although mAbs do not share direct targets or mechanisms of disposition with small‐molecule drugs (SMDs), combining therapeutics of both types can increase the risk of adverse effects and treatment failure. The primary goal of this literature review was identifying mAb‐ASM combinations requiring the attention of professionals who are treating patients with epilepsy. Systematic PubMed and Embase searches (1980–2021) were performed for terms relating to mAbs, ASMs, drug interactions, and their combinations. Additional information was obtained from documents from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Evidence was critically appraised ‐ key issues calling for clinicians' consideration and important knowledge gaps were identified, and practice recommendations were developed by a group of pharmacists and epileptologists. The majority of interactions were attributed to the indirect effects of cytokine‐modulating antibodies on drug metabolism. Conversely, strong inhibitors or inducers of drug‐metabolizing enzymes or drug transporters could potentially interact with the cytotoxic payload of antibody‐drug conjugates, and ASMs could alter mAb biodistribution. In addition, mAbs could potentiate adverse ASM effects. Unfortunately, few studies involved ASMs, requiring the formulation of class‐based recommendations. Based on the current literature, most mAb‐ASM interactions do not warrant special precautions. However, specific combinations should preferably be avoided, whereas others require monitoring and potentially adjustment of the ASM doses. Reduced drug efficacy or adverse effects could manifest days to weeks after mAb treatment onset or discontinuation, complicating the implication of drug interactions in potentially deleterious outcomes. Prescribers who treat patients with epilepsy should be familiar with mAb pharmacology to better anticipate potential mAb‐ASM interactions and avoid toxicity, loss of seizure control, or impaired efficacy of mAb treatment. [ABSTRACT FROM AUTHOR]

Background: Consanguineous kindred presented with an autosomal recessive syndrome of intrauterine growth retardation, marked developmental delay, spastic quadriplegia with profound contractures, pseudobulbar palsy with recurrent aspirations, epilepsy, dysmorphism, neurosensory deafness and optic nerve atrophy with no eye fixation. Affected individuals died by the age of 4. Brain MRI demonstrated microcephaly, semilobar holoprosencephaly and agenesis of corpus callosum. We aimed at elucidating the molecular basis of this disease. Methods: Genome-wide linkage analysis combined with whole exome sequencing were performed to identify disease-causing variants. Functional consequences were investigated in fruit flies null mutant for the DrosophilaSEC31A orthologue. SEC31A knockout SH-SY5Y and HEK293T cell-lines were generated using CRISPR/Cas9 and studied through qRT-PCR, immunoblotting and viability assays. Results: Through genetic studies, we identified a disease-associated homozygous nonsense mutation in SEC31A. We demonstrate that SEC31A is ubiquitously expressed, and that the mutation triggers nonsensemediated decay of its transcript, comprising a practical null mutation. Similar to the human disease phenotype, knockdown SEC31A flies had defective brains and early lethality. Moreover, in line with SEC31A encoding one of the two coating layers comprising the Coat protein complex II (COP-II) complex, trafficking newly synthesised proteins from the endoplasmic reticulum (ER) to the Golgi, CRISPR/Cas9-mediated SEC31A null mutant cells demonstrated reduced viability through upregulation of ER-stress pathways. Conclusion: We demonstrate through human and Drosophila genetic and in vitro molecular studies, that a severe neurological syndrome is caused by a null mutation in SEC31A, reducing cell viability through enhanced ER-stress response, in line with SEC31A's role in the COP-II complex. [ABSTRACT FROM AUTHOR]