Therapy Analysis - Epilepsy
History of epilepsy treatment
Few diseases throughout history have attracted such reverence or stigma to their sufferers as epilepsy. In many ancient cultures, epilepsy was associated with possession by spirits or prophetic experience. The disease is even purported to appear in the Bible in the Gospel of Mark, wherein Christ expels a demon from a young person suffering from seizures. To this day, epileptic attacks are viewed as paranormal experiences in some areas of the world; however, as the Greek physician Hippocrates correctly stated in 400BC, epilepsy has natural causes just like any other illness, and in recent years our understanding of the disease has grown immensely. Accordingly, we have only developed effective anticonvulsant therapeutics relatively recently as well. The first of these was bromide, introduced in 1857 by obstetrician Sir Charles Locock. At the time, preparations of bromide were used as sedatives and were known to have anti-aphrodisiac qualities. As epilepsy was believed to result from sexual excitement, Locock decided to test bromides in the treatment of seizures and, although the reasoning was spurious, the treatment proved effective.
The first major breakthrough in epilepsy therapy came over 50 years later in 1912, with release of the barbituate phenobarbital by Bayer & Co. Phenobarbital was originally used as a sedative and hypnotic, and its anticonvulsant properties were stumbled upon by Alfred Hauptmann, a young physician who used the drug to sedate his epileptic patients. Like other barbituates, phenobarbital affects the neurotransmission of GABA. It is understood to bind to a site on the GABAA receptor and thereby potentiate the effect of GABA. Despite its age, the drug continues to play a significant role in the treatment of epilepsy and is recommended by the WHO as first-line treatment for tonic-clonic seizures (partial and general) in the developing world.
The next milestone in pharmacological intervention came in 1938 with the discovery of phenytoin, the first drug specifically developed for epilepsy. It was discovered by Merritt and Putnam, who developed an animal model to screen for non-sedative anticonvulsant compounds that were structurally related to phenobarbital. It was approved by the US FDA in 1953 and is still used in the treatment of complex partial seizures, general tonic-clonic seizures and seizures during brain surgery. Despite its structural similarity to phenobarbital, phenytoin is believed to function via a separate mechanism, involving blockage of voltage-gated sodium channels in the inactive state, and thus preventing overactivity in the brain.
