The use of Metrazol as a convulsive agent was discovered by the Hungarian-American neurologist and psychiatrist Ladislas J. Meduna in 1934. It works by inhibiting action of GABA, the chief inhibitory neurotransmitter in mammals to induce convulsions.
Meduna was interested in treating schizophrenia and had made an observation that patients that died with epilepsy had more brain glia than patients with schizophrenia. He theorized that by inducing seizures in patients suffering from schizophrenia that it would increase the presence of glia and reverse the mental illness. Meduna attempted to use a few substances to induce seizures such as strychnine and caffeine before testing on animals with a camphor solution.
The camphor solution was tested on patients, mostly catatonic which is considered schizophrenic which upheld his theory. Camphor proved to have a long delay to create a seizure and he discovered the use of pentylenetetrazol (Metrazol), a synthetic preperation of camphor induced an immediate seizure.
His 1937 book, Die Konvulsionstherapie der Schizophrenie recounts how with his treatment of 110 patients that half recovered from schizophrenia. This spurred many mental health centers around the world to adopt this new therapy in their facilities. Metrazol therapies were used only for a few years and fell out of favor with the advent of ECT.
Metrazol produced an explosive seizure about a minute after the injection. Often these convulsions would result in fractured bones and torn muscles. For the therapy to be effective it would be given two of three times a week and a typical course of therapy would be thirty to forty injections. As the patient regained consciousness they would be confused and cooperative with staff which was seen as a marked improvement. Other times in this twilight state the patient would act in a more regressive manner, frightened and scared by the treatment. After a patient received one treatment they were resistant to subsequent treatment, resisting and pleading for it not to be done again and would have to be forcibly treated.
In 1939, Meduna traveled to Chicago's Loyola University to speak and quickly became part of the faculty. He soon lost interest in Metrazol once ECT became more common. "You know this old convulsive therapy is past history for me and I believe for almost every psychiatrist. I do not believe the original publications have much value anymore." He said he preferred ECT to Metrazol "for it's simplicity".
Metrazol's mainstream use lasted from 1936 until 1941 and nearly 37,000 patients underwent the treatment.