A Medicinal Chemistry Perspective on Anticonvulsant Drug Design: Targets, Mechanisms, and Spiro Compounds

The neurological condition known as epilepsy is typified by frequent, unprovoked seizures brought on by aberrant or excessive synchronized neuronal activity in the brain. It can arise from various causes, including brain injury, tumors, infections, immune disorders, or congenital anomalies. However, in many patients, the underlying cause remains unknown. Epileptic seizures are broadly classified into two types: generalized and focal (or partial) seizures. Generalized seizures involve electrical discharges that affect the entire brain, while focal seizures are confined to a specific region. The World Health Organization (WHO) estimates that 50 million individuals worldwide suffer from epilepsy, with low- and middle-income nations accounting for over 80% of cases. In spite of the development of numerous antiepileptic drugs (AEDs), about 30% of individuals with epilepsy suffer from drug-resistant epilepsy (DRE), where seizures remain uncontrolled by current treatments. As a result, the search for new anticonvulsants with improved efficacy and reduced toxicity is a paramount demand. However, target-based drug discovery approaches are relatively uncommon due to limited understanding of the molecular pathways involved in epilepsy and the complex mechanisms of action of most existing AEDs. In this review, we investigate the characteristics of anticonvulsant drugs, the classification of epileptic seizures, the mechanisms through which these drugs exert their effects and spiro compounds with anticonvulsant activity.