Category:Antiepileptics: Difference between revisions

The antiepileptics, also called anticonvulsants or antiseizure medicines, are the medicines used to prevent and control epileptic seizures, and their history, more than that of most classes, is a history of accident. For most of recorded time epilepsy had no effective treatment at all. That changed in 1857, when the English physician Charles Locock told a London medical society that potassium bromide appeared to reduce seizures in a group of his patients. Locock's reasoning was mistaken, he believed epilepsy arose from excessive sexual excitement and gave bromide because it was thought to blunt the sexual drive, but the observation itself held, and potassium bromide became the first genuinely useful antiseizure medicine.^[1]

The next advance was stumbled upon in much the same way. In 1912 the German physician Alfred Hauptmann gave phenobarbital, then a new barbiturate, to his epileptic patients as a sedative to quiet them at night, partly so that he could sleep himself, and saw that those who took it had markedly fewer seizures.^[1] Phenobarbital was more effective than bromide and much better tolerated, and it led the treatment of epilepsy for decades. It remains in use worldwide today, a century after that chance observation, particularly where cost is decisive.

The modern era began in the 1930s with a change of method. Rather than wait for a lucky observation, the American neurologists Houston Merritt and Tracy Putnam built an animal model, an electrically induced seizure in the cat, against which candidate compounds could be tested in series. Screening compounds chemically related to phenobarbital, they found one that suppressed seizures with far less sedation, and in 1938 introduced it as phenytoin.^[2] The achievement was twofold: phenytoin itself, which would treat epilepsy for decades, and the proof that antiseizure medicines could be found by deliberate screening rather than by luck, a method that went on to shape the discovery of medicines well beyond epilepsy.

A first generation followed over the next decades, among them primidone, ethosuximide, carbamazepine, and valproic acid, the last of these, like several before it, found to possess antiseizure activity by chance. From the late twentieth century a second generation arrived, including lamotrigine, levetiracetam, gabapentin, topiramate, and oxcarbazepine. The newer medicines are not, in general, better at controlling seizures than the older ones, but many are better tolerated and interact less with other medicines.^[3] The class shares no single mechanism: it is defined by what its members do, suppress seizures, rather than by how they do it. A seizure is, in broad terms, a burst of excessive and synchronized electrical activity in the brain, and the antiseizure medicines are understood to damp that activity by several different routes, blocking voltage-gated sodium channels, strengthening the inhibitory neurotransmitter GABA, acting on calcium channels, or quieting the release of neurotransmitters.^[3]

Antiepileptics reach well beyond epilepsy: several are mainstays of psychiatry as mood stabilizers, and others treat neuropathic pain and migraine. One caution has come to define the class in modern practice. Several antiepileptics taken during pregnancy raise the risk of birth defects and of later harm to a child's development; the risk is greatest, and clearly dose-dependent, for valproic acid, and for that reason the use of valproate in people who might become pregnant is now sharply restricted.^[4] This category collects the wiki's antiepileptic pages and groups them, as the field does, by generation.

The antiepileptics are conventionally grouped by generation, the order in which they reached use, since the class shares no single mechanism.

• First generation: the agents of the bromide-to-mid-century era. phenobarbital, phenytoin and its prodrug fosphenytoin, primidone, ethosuximide, carbamazepine, and valproic acid.
• Second generation: the agents developed from the 1980s onward, generally better tolerated and with fewer interactions. lamotrigine, levetiracetam, gabapentin, pregabalin, topiramate, oxcarbazepine, lacosamide, zonisamide, vigabatrin, tiagabine, felbamate, eslicarbazepine, and rufinamide.
• Newer agents: brivaracetam, cenobamate, perampanel, and stiripentol.
• Benzodiazepines used in epilepsy: clobazam, clonazepam, and diazepam, indexed here for their antiseizure use; they belong primarily to Benzodiazepines.
• Syndrome-specific agents: cannabidiol and fenfluramine, brought into use for severe childhood epilepsies such as the Dravet and Lennox-Gastaut syndromes.

This category indexes the medicines whose defining action is the suppression of epileptic seizures, grouped above by generation. The boundary is that antiseizure activity, not any single mechanism or chemical family.

Many antiepileptics are used well beyond epilepsy, and are cross-indexed accordingly. Valproic acid, carbamazepine, and lamotrigine are central to psychiatry as mood stabilizers and also appear under Mood Stabilizers; gabapentin, pregabalin, and topiramate are widely used for neuropathic pain and for migraine. The benzodiazepines used in epilepsy are indexed here for that use while belonging primarily to Benzodiazepines. Following the wiki's multi-membership convention, a medicine is indexed wherever its pharmacology and its uses warrant.

Each antiepileptic indexed here has its own page, built on the wiki's standard structure for a medicine: a history-first account, then pharmacology, indications, adverse effects, and interactions. Alongside the generation grouping above, the wiki maintains a set of mechanism-based subcategories, among them sodium channel blockers, GABA enhancers, SV2A ligands, carbonic anhydrase inhibitors, and glutamate/AMPA antagonists, which cut across the generations.

This is one of the wiki's MedCategory class-overview pages. It carries the MedCategory and MedCategoryFull marker tags; the second suppresses the member list that MediaWiki would otherwise generate automatically, leaving the curated index above as the only one. The category sits beneath Medicines and beneath Pharmaceutical, the origin category for medicines that came into use through scientific discovery rather than traditional practice; even the chance discoveries that mark this class were observations made on synthesized compounds in the clinic and the laboratory.