In the 1800's, the basic principles of the nervous system were slowly being unraveled by people such as Galvani in Italy and Helmholtz in Germany.  Toward the end of the 1800s, biologists were approaching an understanding of the details.  In particular, Camillo Golgi (who believed that the nervous system was a single entity) invented a staining technique that allowed Santiago Ramon y Cajal to prove that the nervous system was actually composed of individual neurons.  Together, they won the Nobel Prize in 1906.

The British biologist Sir Charles Sherrington had already named what Ramon y Cajal saw: the synapse.  He, too, would win a Nobel Prize for his work on neurons with Edgar Douglas Adrian.

In 1921, the German biologist Otto Leowi completed the picture by discovering acetylcholine and the idea of the neurotransmitter.  For this work, he received the Nobel Prize, shared with Henry Hallett Dale.  Interestingly, acetylcholine is a relative of muscarine -- the active ingredient of some of those mushrooms that some of our ancient ancestors liked so much.  In 1946, another biologist, von Euler, discovered norepinephrine.  And, in 1950, Eugene Roberts and J. Awapara discovered GABA.

In the early part of the 1900's, we see the beginnings of psychopharmacology as a medical science, with the use of bromide and chloralhydrate as sedatives.  Phenobarbital enters the picture in 1912 as the first barbiturate.  In the second half of the 1900s, with the basic mechanisms of the synapse understood, progress in the development of psychoactive drugs truly got underway.  For example...

In 1949, John Cade, an Australian psychiatrist, found that lithium, a light metal, could lessen the manic aspect of manic-depression.

In 1952, a French Navy Doctor, Henri Laborit, came up with a calming medication which included chlorpromazine, which was promoted as the antipsychotic Thorazine a few years later.

Imipramine, the first tricyclic antidepressant, was developed at Geigy Labs by R. Kuhn in the early 1950's, while he was trying to find a better antihistamine!

In the late 1950's, Nathan Klein studied the use of reserpine in 1700s India, and found it reduced the symptoms of many of his psychiatric patients.  Unfortunately, the side effects were debilitating.

In 1954, the drug meprobamate, better known as Miltown, became available on the market.  Its chemical foundation was discovered a decade earlier by Frank Berger, while he was trying to discover a new antibiotic. He found a tranquilizer instead!

Iproniazid (an MAOI antidepressant) was developed in 1956 by the Hoffman-LaRoche pharmaceutical company for tuberculosis patients.  It appeared to cheer them up a bit!  Although it was banned because of side effects, it was the first in a long series of antidepressants.

Leo Sternbach also worked for Hoffman-LaRoche, and discovered the drug Valium (diazepam) in 1959, and Librium (chlordiazepoxide) the following year -- two of the most useful and used psychoactive drugs ever.

The progress of psychopharmacology was greatly aided by increased knowledge of the activities at the level of the synapse.  John Eccles, Alan Lloyd Hodgkin and Andrew Fielding Huxley shared the Nobel Prize in 1963 for their work on the neuron's membrane.  And in 1973, Solomon Snyder and Candace Pert of Johns Hopkins discovered "internal morphine" or endorphin, and the "lock-and-key" theory -- the basic mechanism of psychoactive drugs -- was confirmed.

In 1974, D. T. Wong at Eli Lilly labs discovered fluoxetine -- Prozac -- and its antidepressant effects. It was approved by the FDA in 1987. This substance and others like it -- known as the serotonin selective re-uptake inhibitors or SSRIs -- would dramatically change the care of people with depression, obsessive-compulsive disorder, social anxiety, and other problems.

In the 1990's, new neuroleptics (antipsychotic drugs) such as clozapine were developed which addressed the problems of schizophrenia more completely than the older drugs such as chlorpromazine, and with fewer side effects.

What is the future going to be like, in regard to psychopharmacology? Some say the major breakthroughs are over, and it is just a matter of producing better variations. But that has been said many times before. Biochemistry is still progressing, and every year brings something new. The rest of us can only hope that many more and better medications with psychiatric applications will be found.