03.18.07
A Brief History of the Discovery and Development of Anti-Depressants
There is still a lot that is not understood about depression. It was only in 1952 that the first drug to affect depression was discovered accidentally by Henri Laborit, Jean Delay, and Pierre Deniker. They had noticed that an antihistamine, chlorpromazine, would calm schizophrenic patients. Because of this, Geigy Pharmaceuticals, the makers of chlorpromazine, modified the structure of the chlorpromazine molecule to try and eliminate its antihistamine activity and other side effects. The result was later tested in schizophrenic patients. Here’s a quote taken from Pills, Potions, and Poison regarding the result of that first experiment:
“The whole team of medical and nursing staff waited with bated breath. At first, very little happened. Then, within a period ranging from a few days to several weeks, certain very definite results bagan to appear. These were not only fascinating. They were, in some patients, quite alarming. Several previously quiet patients began to deteriorate with increasing agitation. One man, in such a state, managed to get hold of a bicycle and rode in his nightshirt to a nearby village singing lustily, much to the alarm of the local inhabitants. Our disappointment was intense. The trial was abandoned.”
The results gathered from the test above revealed that the patients who showed the greatest development of agitation and excitement where those who had been “depressed” as well as schizophrenic. That spurred the idea to try the drug on patients who were “only depressed.” Here is another excerpt by Alan Broadhurst of the Geigy team from the book describing the results of the modified drug tested on “depressed” patients in 1955:
“After forty patients had been treated, it was clear that G22355 [the company's code name for the drug] was producing a dramatic, and this time beneficial, response. I had seen some seriously depressed patients, and I was all too aware of what a merciless and devastating illness severe and unremitting depression could be. The fact that we might now, for the first time ever, have an effective treatment seemed incredible. If this therapeutic effect could be repeated in larger groups of patients, then G22355 represented a major advance in medicine.”
G22355 later became known as Imipramine, and later followed by other drugs called “tricyclic antidepressants” because the molecules all contain three rings of atoms. A second drug that was also accidentally discovered was Iproniazid, which was used to treat tuberculosis, but found to make the patients feel “happier.”
At this point, it was still not known what caused depression, only that there were some drugs which seemed to reverse it. One of the first clues of what might be linked to depression was found by observing patients who used Reserpine, a drug given to lower blood pressure in hypertensive patients. In addition to lowering blood pressure, these patients got severly depressed, some even suicidal. From understanding the action of Reserpine, it was deduced that depression might be linked to reduced release of norepinephrine from nerve cells. It was known that Reserpine lowered blood pressure by causing the sympathetic nerves to lose their stores of the neurotransmitter norepinephrine (noradrenaline). Normally, the nerve stores norepinephrine in small packets known as vesicles which are secreted onto receptors on blood vessels when the nerves are active. Reserpine disrupts the vesicles so that norepinephrine can no longer be stored or released, the sympathetic stimulation of the heart and blood vessels decreases and the blood pressure falls.
Stone and Darlington, authors of Pills, Potions, and Poisons, wrote that the drugs which had been found accidentally to benefit depressed patients also affected norepinephrine neurons in the brain.
Next post on “depression” and “anti-depressants” will touch on the amines and receptors in relation to depression.
Marlakins
book » The Sadness of Spimes said,
March 26, 2007 at 1:11 am
[...] A Brief History of the Discovery and Development of Anti-Depressants There is still a lot that is not understood about depression. It was only in 1952 that the first drug to affect depression was discovered accidentally by Henri Laborit, Jean Delay, and Pierre Deniker. They had noticed that an antihistamine, chlorpromazine, would calm schizophrenic patients. Because of this, Geigy Pharmaceuticals, the makers of chlorpromazine, modified the structure of the chlorpromazine molecule to try and eliminate its antihistamine activity and other side effects. The result was later tested in schizophrenic patients. Here s a quote taken from Pills, Potions, and Poison regarding the result of that first experiment: The whole team of medical and nursing staff waited with bated breath. At first, very little happened. Then, within a period ranging from a few days to several weeks, certain very definite results bagan to appear. These were not only fascinating. They were, in some patients, quite alarming. Several previously quiet patients began to deteriorate with increasing agitation. One man, in such a state, managed to get hold of a bicycle and rode in his nightshirt to a nearby village singing lustily, much to the alarm of the local inhabitants. Our disappointment was intense. The trial was abandoned. The results gathered from the test above revealed that the patients who showed the greatest development of agitation and excitement where those who had be depressed as well as schizophrenic. That spurred the idea to try to drug on patients who were only depressed. Here is another excerpt Alan Broadhurst of the Geigy team from the book describing the results of the modified drug tested on depressed patients in 1955: After forty patients had been treated, it was clear that G22355 [the company s code name for the drug] was producing a dramatic, and this time beneficial, response. I had seen some seriously depressed patients, and I was all too aware of what a merciless and devastating illness severe and unremitting depression could be. The fact that we might now, for the first time ever, have an effective treatment seemed incredible. If this therapeutic effect could be repeated in larger groups of patients, then G22355 represented a major advance in medicine. G22355 later became known as Imipramine, and later followed by other drugs called tricyclic antidepressants because the molicules all contain three rings of atoms. A second drug that was also accidentally discovered was Iproniazid, which was used to treat tuberculosis, but found to make the patients feel happier. At this point, it was still not known what caused depression, only that there were some drugs which seemed to reverse it. One of the first clues of what might be linked to depression was found by observing patients who used Reserpine, a drug given to lower blood pressure in hypertensive patients. In addition to lowering blood pressure, these patients got severly depressed, some even suicidal. From understanding the action of Reserpine, it was deduced that depression might be linked to reduced release of norepinephrine from nerve cells. It was known that Reserpine lowered blood pressure by causing the sympathetic nerves to lose their stores of the neurotransmitter norepinephrine (noradrenaline). Normally, the nerve stores norepinephrine in small packets known as vesicles which are secreted onto receptors on blood vessels when the nerves are active. Reserpine disrupts the vesicles so that norepinephrine can no longer be stored or released, the sympathetic stimulation of the heart and blood vessels decreases and the blood pressure falls. Stone and Darlington, authors of Pills, Potions, and Poisons, wrote that the drugs which had been found accidentally to benefit depressed patients also affected norepinephrine neurons in the brain. Next post on depression and anti-depressants will touch on the amines and receptors in relation to depression. Marlakins [...]