From barbiturates to ganaxolone: The importance of chirality in drug development and in understanding the actions of old and new antiseizure medications

Pharmacology & Therapeutics, Journal Year: 2025, Volume and Issue: unknown, P. 108808 - 108808

Published: Feb. 1, 2025

Out of 37 antiseizure medications (ASMs) currently in the market, 17 are chiral molecules and an additional one (oxcarbazepine) is a prodrug compound licarbazepine. Of ASMs, six (ethosuximide, fenfluramine, methsuximide, mephobarbital, stiripentol vigabatrin) marketed as racemates, remainder licensed enantiomerically pure medicines. note, all ASMs introduced prior to 1990 were racemates. Stiripentol, fenfluramine vigabatrin only racemic approved by FDA >10 years after release regulatory guidelines on development Despite fact that pharmacokinetic pharmacodynamic differences between enantiomers have been recognized for decades, importance chirality understanding biological actions not widely appreciated, many recent publications refer these if they single molecular entity. In present article, we provide critical review developed 1920s, when mephobarbital was introduced, 2022, last ASM (ganaxolone) approved. We summarize available data stereoselective pharmacokinetics pharmacodynamics also discuss aspects related introduction medicines within current scenario Europe U.S., focusing stiripentol, examples different approaches. identified number knowledge gaps relevant use drugs epilepsy, including remarkable lack published information comparative pharmacokinetics, toxicity activity most ASMs. The clinical discussed, together with rationale follow-up compounds potentially improved efficacy, safety commercial viability.

Language: Английский

A rapid and sensitive paper-based immunoassay for fenfluramine detection in slimming foods

Microchemical Journal, Journal Year: 2025, Volume and Issue: unknown, P. 113118 - 113118

Published: Feb. 1, 2025

Language: Английский

Evaluating bexicaserin for the treatment of Developmental Epileptic Encephalopathies

Expert Opinion on Pharmacotherapy, Journal Year: 2024, Volume and Issue: 25(9), P. 1121 - 1130

Published: June 12, 2024

Developmental epileptic encephalopathies (DEEs) pose significant challenges due to their refractory nature and limited treatment options. Despite advancements in genetic understanding, effective therapies targeting underlying pathophysiology are lacking. Serotoninergic dysfunction has been implicated epilepsy, sparking interest serotonin as a therapeutic target.

Language: Английский