Epileptic Targets and Drugs: A Mini-Review

Rodrigues, Teresa Carolliny Moreira Lustoza; Moura, Jéssica Paiva de; Santos, Aline Matilde Ferreira dos; Monteiroa, Alex France M; Lopes, Simone Mendes; Scotti, Marcus T.; Scotti, Luciana

doi:10.2174/1389450123666220927103715

Cited by 3 publications

(1 citation statement)

References 70 publications

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“…Many treatments to fight epileptic seizures and epilepsy in general have been developed and applied over time and many efforts are still currently spent to exploit new therapeutic strategies. However, going into more detail on the pharmacology of epilepsies caused by Nav channels is not within the scope of this review; regarding this subject, it is possible to consult more exhaustive reviews [ 49 , 50 ].…”

Section: Vgsc Associated Neurological Disorders: Channelopathiesmentioning

confidence: 99%

Voltage-Gated Sodium Channel Dysfunctions in Neurological Disorders

Barbieri

Nizzari

Zanardi

et al. 2023

Life

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The pore-forming subunits (α subunits) of voltage-gated sodium channels (VGSC) are encoded in humans by a family of nine highly conserved genes. Among them, SCN1A, SCN2A, SCN3A, and SCN8A are primarily expressed in the central nervous system. The encoded proteins Nav1.1, Nav1.2, Nav1.3, and Nav1.6, respectively, are important players in the initiation and propagation of action potentials and in turn of the neural network activity. In the context of neurological diseases, mutations in the genes encoding Nav1.1, 1.2, 1.3 and 1.6 are responsible for many forms of genetic epilepsy and for Nav1.1 also of hemiplegic migraine. Several pharmacological therapeutic approaches targeting these channels are used or are under study. Mutations of genes encoding VGSCs are also involved in autism and in different types of even severe intellectual disability (ID). It is conceivable that in these conditions their dysfunction could indirectly cause a certain level of neurodegenerative processes; however, so far, these mechanisms have not been deeply investigated. Conversely, VGSCs seem to have a modulatory role in the most common neurodegenerative diseases such as Alzheimer’s, where SCN8A expression has been shown to be negatively correlated with disease severity.

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Section: Vgsc Associated Neurological Disorders: Channelopathiesmentioning

confidence: 99%

Voltage-Gated Sodium Channel Dysfunctions in Neurological Disorders

Barbieri

Nizzari

Zanardi

et al. 2023

Life

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Design and synthesis of novel GluN2A NMDAR positive allosteric modulators via scaffold hopping strategy as anti-stroke therapeutic agents

Chen

Zhu

liu

et al. 2023

Bioorganic & Medicinal Chemistry

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Multi-target Phenylpropanoids Against Epilepsy

Rodrigues,

Dias,

dos Santos

et al. 2024

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Epilepsy is a neurological disease with no defined cause, characterized by recurrent epilep- tic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phe- nylpropanoid compounds to predict biological activities. The LBVS were developed for the targets al- pha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel T- type (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 com- pound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and sig- nificant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epi- lepsy.

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Epileptic Targets and Drugs: A Mini-Review

Cited by 3 publications

References 70 publications

Voltage-Gated Sodium Channel Dysfunctions in Neurological Disorders

Voltage-Gated Sodium Channel Dysfunctions in Neurological Disorders

Design and synthesis of novel GluN2A NMDAR positive allosteric modulators via scaffold hopping strategy as anti-stroke therapeutic agents

Multi-target Phenylpropanoids Against Epilepsy

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