How did phenobarbital’s chemical structure affect the development of subsequent antiepileptic drugs (AEDs)?

Bialer, Meir

doi:10.1111/epi.12024

Cited by 25 publications

(10 citation statements)

References 45 publications

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“…The anti-absence drug ethosuximide, with calcium blocking properties, was also discovered at this stage due to its structural similarity to phenytoin (22). It has been said that ethosuximide could trigger generalised tonic-clonic seizures while phenytoin can boost the tendency to absences (23).…”

Section: Modern Neuroscience Emergesmentioning

confidence: 99%

Slump, tilfeldigheter og antiepileptika

Nakken¹,

Brodtkorb²

2017

Tidsskriftet

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Section: Modern Neuroscience Emergesmentioning

confidence: 99%

Slump, tilfeldigheter og antiepileptika

Nakken¹,

Brodtkorb²

2017

Tidsskriftet

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“…Ethosuximide, a succinimide derivative that resembles phenobarbital, is currently regarded as the first-line drug for the symptomatic treatment of absence seizures (Bialer 2012b;Glauser et al, 2013b;Dezsi et al, 2013). Chemically, it is the R,S-2-ethyl-2methyl-succinimide (Fig.…”

Section: Ethosuximidementioning

confidence: 99%

Chiral chromatographic resolution of antiepileptic drugs and their metabolites: a challenge from the optimization to the application

Fortuna

Alves

2013

Biomedical Chromatography

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A large number of the antiepileptic drugs (AEDs) presently available for clinical practice are chiral compounds while others, although achiral, may originate pharmacologically active chiral metabolites in vivo. The well-known implications of chirality in pharmacokinetics and pharmacodynamics demand the investigation of pharmacological properties for a racemic mixture and each enantiomer. To achieve these objectives, appropriate chiral analytical methods must be available. This article provides the first review of the current state of the art in chiral chromatographic methods available for quantifying enantiomers of AEDs in distinct matrices. Particular attention is paid to the methodological aspects and optimization strategies that successfully allow enantiomeric chromatographic separation of chiral AEDs and/or metabolites. Furthermore, the relevance of these methods in supporting the discovery and development of chiral AEDs is emphasized. In parallel and whenever available, the principal validation parameters are herein considered and related to the stage of drug discovery and development. In an attempt to optimize anticonvulsant activity and simultaneously diminish toxic effects, many pharmaceutical companies have started to manufacture single enantiomers. Therefore, chiral chromatographic techniques will be essential and the information herein compiled can be used as a framework for developing them.

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“…This was the age of medicinal chemistry when drug structures could be manipulated. The chemical structure of phenobarbital spawned an entire range of related drugs (Bialer, 2012). Of these, the most important were perhaps primidone, methylphenobarbital, amylobarbital, the thiobarbiturates, the hydantoins, and the succinimides.…”

Section: Phenobarbital In 1940–1975mentioning

confidence: 99%

“…We consider only the clinical aspects. Phenobarbital has had a major effect on the medicinal chemistry of epilepsy, influencing drug discovery and the experimental aspects of epilepsy; these issues are covered in the accompanying articles in this supplement (Bialer, 2012; Löscher & Rogawski, 2012).…”

mentioning

confidence: 99%

How phenobarbital revolutionized epilepsy therapy: The story of phenobarbital therapy in epilepsy in the last 100 years

Yasiry

Shorvon

2012

Epilepsia

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Summary Phenobarbital (phenobarbitone) was first used as an antiepileptic drug 100 years ago, in 1912. This article tells the story of the discovery of its antiepileptic action, its early development, and the subsequent course of its clinical use over the 100‐year period. The side effects, pharmacokinetics, and misuse of barbiturates are considered, along with the more recent clinical trials and the drug’s current clinical utilization. The introduction of controlled drug regulations, the comparative cost of phenobarbital, and its inclusion on the World Health Organization (WHO) essential drug list are discussed. It is one of the few drugs on the formulary in 1912 that is still listed today, and remarkably its efficacy in epilepsy has not been significantly bettered. The current recommendation by the WHO is that phenobarbital should be offered as the first option for therapy for convulsive epilepsy in adults and children if availability can be ensured. This is rated as a strong recommendation because of the proven efficacy and low cost of phenobarbital, and despite its perceived side‐effect profile and the practical problems of access. Whether this recommendation puts “a hierarchy on the brain,” as has been suggested, is arguable. Much still needs to be learned about the drug’s effects, and the issues raised by phenobarbital have lessons for all antiepileptic drug therapy.

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How did phenobarbital’s chemical structure affect the development of subsequent antiepileptic drugs (AEDs)?

Cited by 25 publications

References 45 publications

Slump, tilfeldigheter og antiepileptika

Slump, tilfeldigheter og antiepileptika

Chiral chromatographic resolution of antiepileptic drugs and their metabolites: a challenge from the optimization to the application

How phenobarbital revolutionized epilepsy therapy: The story of phenobarbital therapy in epilepsy in the last 100 years

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