ArticleScientific reports2022
Efflux dynamics of the antiseizure drug, levetiracetam, through the P-glycoprotein channel revealed by advanced comparative molecular simulations.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 citations in OpenAlex.
- Transfer of anticonvulsants and lithium into amniotic fluid, umbilical cord blood & breast milk: A systematic review & combined analysis.Progress in neuro-psychopharmacology & biological psychiatry · 2023Pooled it
- Genomic and molecular dynamics analysis of mefA-encoded macrolide efflux protein from Tn2009 and Tn2010 in Streptococcus pneumoniae.Molecular genetics and genomics : MGG · 2026Article
- Drug-resistant Epilepsy: Which Drugs are Substrates of P-glycoprotein and Which are Not?Current neuropharmacology · 2026Review
- The intersection of circadian rhythms and the blood-brain barrier with drug efficacy and delivery in neurological disorders.Advanced drug delivery reviews · 2025Review
- A Revolutionary Approach for Combating Efflux Transporter-mediated Resistant Epilepsy: Advanced Drug Delivery Systems.Current pharmaceutical design · 2025Review
- Mechanistic insights into P-glycoprotein ligand transport and inhibition revealed by enhanced molecular dynamics simulations.Computational and structural biotechnology journal · 2024Article
- ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Effects of plateau hypoxia on pharmacokinetic parameters and cerebral-blood distribution of levetiracetam in rats.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Targeting Staphylococcal Cell-Wall Biosynthesis Protein FemX Through Steered Molecular Dynamics and Drug-Repurposing Approach.ACS omega · 2023Article
- Investigation of molecular details of a bacterial cationic amino acid transporter (GkApcT) during arginine transportation using molecular dynamics simulation and umbrella sampling techniques.Journal of molecular modeling · 2023Article
- The Alternating Access Mechanism in Mammalian Multidrug Resistance Transporters and Their Bacterial Homologs.Membranes · 2023Article
- Recent Advances on P-Glycoprotein (ABCB1) Transporter Modelling with In Silico Methods.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the precise mechanistic details of the possible binding and transport of antiseizure medications (ASMs) through the P-glycoprotein (P-gp) efflux pump is essential to find strategies for the treatment of patients with epilepsy resistant to ASMs. In the present work, conventional molecular dynamics, binding free energy calculations, steered molecular dynamics and umbrella sampling were applied to study the interactions of levetiracetam and brivaracetam with P-gp and their possible egress path from the binding site. Comparative results for the control drugs, zosuquidar and verapamil, confirmed their established P-gp inhibitory activity. Brivaracetam, a non-substrate of P-gp, demonstrated stronger static and dynamic interactions with the exporter protein, than levetiracetam. The potential of mean force calculations indicated that the energy barriers through the ligand export were the lowest for levetiracetam, suggesting the drug as a P-gp substrate with facile passage through the transporter channel. Our findings also stressed the contribution of nonpolar interactions with P-gp channel lining as well as with membrane lipid molecules to hamper the ASM efflux by the transmembrane exporter. Appropriate structural engineering of the ASMs is thus recommended to address drug-resistant epilepsy.
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