4.6 Review

Levetiracetam Mechanisms of Action: From Molecules to Systems

Journal

PHARMACEUTICALS
Volume 15, Issue 4, Pages -

Publisher

MDPI
DOI: 10.3390/ph15040475

Keywords

levetiracetam; antiepileptic drugs; SV2A; neuroprotection; neuroinflammation; GABAergic system; calcium homeostasis

Funding

  1. Instituto Nacional de Pediatria [INP C-002/2017, 031/2018]
  2. Conacyt (CB 2017-2018) [A-S1-17090]
  3. Secretaria de Investigacion y Posgrado-Instituto Politecnico Nacional [SIP-IPN 20210459]

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This study provides a comprehensive review of levetiracetam, discussing its clinical uses, structural properties, therapeutic targets, and various molecular, genetic, and systemic action mechanisms, highlighting its potential as a candidate for drug repurposing.
Epilepsy is a chronic disease that affects millions of people worldwide. Antiepileptic drugs (AEDs) are used to control seizures. Even though parts of their mechanisms of action are known, there are still components that need to be studied. Therefore, the search for novel drugs, new molecular targets, and a better understanding of the mechanisms of action of existing drugs is still crucial. Levetiracetam (LEV) is an AED that has been shown to be effective in seizure control and is well-tolerable, with a novel mechanism of action through an interaction with the synaptic vesicle protein 2A (SV2A). Moreover, LEV has other molecular targets that involve calcium homeostasis, the GABAergic system, and AMPA receptors among others, that might be integrated into a single mechanism of action that could explain the antiepileptogenic, anti-inflammatory, neuroprotective, and antioxidant properties of LEV. This puts it as a possible multitarget drug with clinical applications other than for epilepsy. According to the above, the objective of this work was to carry out a comprehensive and integrative review of LEV in relation to its clinical uses, structural properties, therapeutical targets, and different molecular, genetic, and systemic action mechanisms in order to consider LEV as a candidate for drug repurposing.

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