ReviewFrontiers in pharmacology2021
Single-Target Versus Multi-Target Drugs Versus Combinations of Drugs With Multiple Targets: Preclinical and Clinical Evidence for the Treatment or Prevention of Epilepsy.
Review in Frontiers in pharmacology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 121 citations in OpenAlex.
- Large-scale comparative virtual screening identifies novel molecular targets underlying the multi-target activity of quercetin in psoriasis.Inflammopharmacology · 2026Article
- Phenytoin Derivatives as Antagonists of AMPA Receptors and Voltage-Gated Sodium Channels: A Structure-Function Study.International journal of molecular sciences · 2026Article
- Antiseizure Medications in Development: Novel Mechanisms, Precision Therapy, and the Move Towards Disease Modification.Current issues in molecular biology · 2026Review
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- Combined metformin and Taurine attenuate age-related bone loss.Molecular biology reports · 2026Article
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- Novel 3-Methoxypropanamide Derivatives as Potential Antiseizure and Antinociceptive Agents: Experimental Evidence from In Vitro and In Vivo Studies.Journal of medicinal chemistry · 2026Article
- Distributed Pharmacodynamic Architecture in Multi-Component Herbal Formulations: A Flux-Based Framework for Redox-Heterogeneous Diseases.Pharmaceutics · 2026Review
- Redox-Guided Epigenetic Signaling in Cancer: miRNA-DNMT Feedback Loops as Epigenetic Memory Modulates.Antioxidants (Basel, Switzerland) · 2026Review
- Modular Model of Neuronal Activity That Captures the Dynamics of Main Molecular Targets of Antiepileptic Drugs.International journal of molecular sciences · 2026Article
- Polysaccharide-rich birch sap attenuates kainic acid-induced acute seizures by suppressing TLR4/NF-κB-mediated inflammation and preserving blood-brain barrier and glutamate homeostasis.Frontiers in pharmacology · 2026Article
- Computational Design of Drugs for Epilepsy using a Novel Guided Evolutionary Algorithm for Enhanced Blood Brain Barrier Permeability.Central nervous system agents in medicinal chemistry · 2026Article
- Molecular Basis of GABA Aminotransferase Inhibition in Epilepsy: Structure, Mechanisms, and Drug Development.Current issues in molecular biology · 2025Review
- Article
- Carbogen Inhalation Therapy for Epileptic Seizures: Mechanisms, Evidence, and Future Directions.CNS neuroscience & therapeutics · 2025Review
- Discovery of a "First-in-Class" Selective Multikinase (CDK4/6/9-AURKA/B) Inhibitor, LCI133, for Neuroblastoma.Journal of medicinal chemistry · 2025Article
- Exploiting the 2-(1,3,4,9-tetrahydropyrano[3,4-Journal of medicinal chemistry · 2025Article
- Engineering Bispecific Peptides for Precision Immunotherapy and Beyond.International journal of molecular sciences · 2025Review
- Transgenic mouse models of sodium and potassium channelopathies in epilepsy: insights into disease mechanisms and therapeutics.Bioscience reports · 2025Review
- Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rationally designed multi-target drugs (also termed multimodal drugs, network therapeutics, or designed multiple ligands) have emerged as an attractive drug discovery paradigm in the last 10-20 years, as potential therapeutic solutions for diseases of complex etiology and diseases with significant drug-resistance problems. Such agents that modulate multiple targets simultaneously are developed with the aim of enhancing efficacy or improving safety relative to drugs that address only a single target or to combinations of single-target drugs. Although this strategy has been proposed for epilepsy therapy >25 years ago, to my knowledge, only one antiseizure medication (ASM), padsevonil, has been intentionally developed as a single molecular entity that could target two different mechanisms. This novel drug exhibited promising effects in numerous preclinical models of difficult-to-treat seizures. However, in a recent randomized placebo-controlled phase IIb add-on trial in treatment-resistant focal epilepsy patients, padsevonil did not separate from placebo in its primary endpoints. At about the same time, a novel ASM, cenobamate, exhibited efficacy in several randomized controlled trials in such patients that far surpassed the efficacy of any other of the newer ASMs. Yet, cenobamate was discovered purely by phenotype-based screening and its presumed dual mechanism of action was only described recently. In this review, I will survey the efficacy of single-target vs. multi-target drugs vs. combinations of drugs with multiple targets in the treatment and prevention of epilepsy. Most clinically approved ASMs already act at multiple targets, but it will be important to identify and validate new target combinations that are more effective in drug-resistant epilepsy and eventually may prevent the development or progression of epilepsy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.