A Review of Phenytoin Used as an Antiarrhythmic Agent

Phenytoin, a hydantoin derivative, is primarily used as an anticonvulsant and has been recognized for its antiarrhythmic potential for a long time. Phenytoin has been classified as a Class IB antiarrhythmic agent according to the Vaughan Williams classification. Cardiac arrhythmias lead to sudden Death hence there is necessities to synthesize effective and safer therapeutic agents. This review highlights the chemical structure, physicochemical properties, pharmacokinetics, and antiarrhythmic activity of phenytoin with its gap analysis. Emphasis is placed on experimental models used to evaluate antiarrhythmic activity, particularly barium chloride– and adrenaline-induced arrhythmias in Wistar rats, with assessment through electrocardiogram and blood pressure measurements. Additionally, the role of oxime and amidoxime derivatives in cardiovascular therapy is discussed, given their vasorelaxation, antiplatelet, and antihypertensive properties. Molecular docking studies targeting the human cardiac sodium channel (Nav1.5) further support the potential of these compounds as sodium channel blockers. Despite its clinical usefulness, phenytoin is limited by a narrow therapeutic index, drug interactions, and toxicity. The synthesis and evaluation of novel phenytoin derivatives and oxime-based compounds may offer safer and more effective alternatives for the management of refractory ventricular arrhythmias.