ReviewJournal of neurology2017
Phenytoin: 80 years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action.
Review in Journal of neurology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Cerebellar Degeneration in Epilepsy: A Systematic Review.International journal of environmental research and public health · 2021Pooled it
- Electrospun bi-layer carboxymethyl cellulose/polyvinyl alcohol/polycaprolactone nanofibers: fabrication, degradation, and phenytoin release kinetics.Scientific reports · 2026Article
- Co-Selection of Low Cadmium Accumulation and High Yield During Tomato Improvement.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Conotoxins Targeting Voltage-Gated Sodium Ion Channels.Pharmacological reviews · 2024Review
- Antiepileptic drug-loaded and multifunctional iron oxide@silica@gelatin nanoparticles for acid-triggered drug delivery.Scientific reports · 2024Article
- Intranasal delivery of phenytoin loaded layered double hydroxide nanoparticles improves therapeutic effect on epileptic seizures.Journal of nanobiotechnology · 2024Article
- Significance of Oral Manifestations in the Diagnosis of Severe Phenytoin-Induced Thrombocytopenia: A Rare Case.Cureus · 2023Article
- Synthesis, computational study and biological evaluation of 9-acridinyl and 1-coumarinyl-1,2,3-triazole-4-yl derivatives as topoisomerase II inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- From HDAC to Voltage-Gated Ion Channels: What's Next? The Long Road of Antiepileptic Drugs Repositioning in Cancer.Cancers · 2022Review
- Phenytoin Regulates Migration and Osteogenic Differentiation by MAPK Pathway in Human Periodontal Ligament Cells.Cellular and molecular bioengineering · 2022Article
- No Detectable Phenytoin Plasma Levels After Topical Phenytoin Cream Application in Chronic Pain: Inferences for Mechanisms of Action.Journal of pain research · 2022Article
- Phenytoin Is Promoting the Differentiation of Dental Pulp Stem Cells into the Direction of Odontogenesis/Osteogenesis by Activating BMP4/Smad Pathway.Disease markers · 2022Article
- The Pharmacology and Clinical Efficacy of Antiseizure Medications: From Bromide Salts to Cenobamate and Beyond.CNS drugs · 2021Review
- Oral Use of Phenytoin to Reduce Calcification in Bovine Pericardium and Porcine Aortic Leaflets Implants in Rats.Brazilian journal of cardiovascular surgery · 2021Article
- Inhibition of Death-associated Protein Kinase 1 protects against Epileptic Seizures in mice.International journal of biological sciences · 2021Article
- Screening for Activity Against AMPA Receptors Among Anticonvulsants-Focus on Phenytoin.Frontiers in pharmacology · 2021Article
- Membrane Stabilizer Medications in the Treatment of Chronic Neuropathic Pain: a Comprehensive Review.Current pain and headache reports · 2019Review
- Lidocaine and carbamazepine inhibit while phenytoin and lamotrigine paradoxically enhance the insect neuromuscular transmission.Invertebrate neuroscience : IN · 2019Article
- Phenytoin Cream for the Treatment for Neuropathic Pain: Case Series.Pharmaceuticals (Basel, Switzerland) · 2018Article
- Phenytoin: a step by step insight into its multiple mechanisms of action-80 years of mechanistic studies in neuropharmacology.Journal of neurology · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In 1908 phenytoin (5,5-diphenylhydantoin) was first synthesized as a barbiturate derivative in Germany by professor Heinrich Biltz (1865-1943) and subsequently resynthesized by an American chemist of the pharmaceutical company Parke-Davis in 1923 in Detroit. Screening phenytoin did not reveal comparable sedative side effects as barbiturates and, thus, Parke-Davis discarded this compound as a useful drug. In 1936, phenytoin's anticonvulsive properties were identified via a new animal model for convulsive disorders, developed by Putnam and Merritt, who also evaluated its clinical value in a number of patients in the period 1937-1940. For many diseases, mechanism of action of phenytoin remains obscure. The voltage-gated sodium channel was and is generally regarded as the main target to explain phenytoin's activity as an anticonvulsant and an anti-arrhythmic drug. This target, however, does not explain many of the other clinical properties of phenytoin. We will explore a number of original articles on phenytoin published in its 80 years history and give extra attention to the various hypothesis and experiments done to elucidate its mechanisms of action. Phenytoin has been explored in over 100 different disorders; the last two promising indications tested in the clinic are breast cancer and optic neuritis. Most probably, there are multiple targets active for these various disorders, and the insight into which targets are relevant is still very incomplete. It is remarkable that many pharmacological studies tested one dose only, mostly 50 or 100 μM, doses which most probably are higher than the non-plasma bound phenytoin plasma levels obtained during treatment.
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What OpenQuestion holds
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.