Considered a breakthrough medication, Thorazine secured FDA approval on March 26, 1954 as the first psychiatric medication. Prior to Thorazine’s inception, mental illnesses were treated with psycho- and electroshock therapies and institutionalization. The lobotomy was also popular (its inventor, Egaz Moniz, received the 1941 Nobel Prize in Medicine).
Change came when psychiatry finally crossed paths with the rest of medicine. Following in the footsteps of Paul Ehrlich, a German scientist who discovered a cure for syphilis, researchers all over the world were looking for compounds— “magic bullets”— to cure other diseases that plagued humanity.
Thorazine, generic name Chlorpromazine, was the result of researchers in France trying to find a “magic bullet” for malaria. Instead, they found a sedative thought to be potentially useful in surgery. They also discovered that it produced “a medicinal lobotomy.”
And why do with surgery what you could do with drugs?
Thorazine works by blocking dopamine receptors in the brain. In response, the presynaptic neurons release more dopamine into the synaptic cleft, stimulating the postsynaptic neuron to increase dopamine receptor density.
If this is sounding counter-intuitive to anyone, you are right. Blocking the receptors does just means that there is more dopamine around and more receptors to respond to it. (If this is sounding confusing to anyone, click here).
But, after three weeks, the feedback mechanism that regulates dopamine release based on the activity of the post-synaptic neuron (which is suppressed because Thorazine blocks its receptors) begins to fail. This means that the neurons begin to fire in irregular patterns or stop firing all together.
The problem with this? Dopamine doesn’t just make you psychotic, it makes your muscles move. Parkinson’s disease is caused by the death of neurons in the brain that use dopamine as their transmitter. Which brings us to the unpleasant side effects that lead Thorazine to fall out of favour, including but not limited to: constipation, sedation, low blood pressure, restlessness and the inability to stop moving, sustained muscle contractions and twitching, and tardive dyskinesia.
Tardive dyskinesia is irreversible and characterized by repetitive involuntary movements like grimacing, tongue protrusion, lip smacking, puckering and pursing of the lips and rapid eye blinking.
This might not seem so bad if you are already suffering from “senile agitation” like the poor man in this ad, but the National Institute of Health is currently reporting that in older adults suffering from dementia, Thorazine poses and increased risk of death.
Sometimes learning the history of something ruins it a little bit… next week: A Short History of Surgery! (Just kidding.)
For more information on this and other psychiatric drugs, read Robert Whitaker’s Anatomy of an Epidemic.