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As late as the 1950s, it was assumed that communication between nerve cells in the brain occurred predominantly, if not entirely, by electrical impulses. A decade later, the theory of chemical transmission, which until then had been thought to occur only in the peripheral nervous system, had gained strong entrance for the central nervous system. This paradigm shift opened up an enormous new perspective in brain research, not least by facilitating the study of brain function by means of chemical tools, which in different ways could modify the chemical signaling between nerve cells. Moreover, such tools sometimes turned out to be useful as therapeutic agents. Thus for the first time, a variety of disorders in the central nervous system could be treated effectively.
REVIEW: NEUROSCIENCE
In 1955 and '56, I took a sabbatical in Bernard B. Brodie's famous Laboratory of Chemical Pharmacology at the National Heart Institute in Bethesda, Maryland, during a very dramatic period in which drug research was undergoing a revolution and neuropsychopharmacology was in statu nascendi. This was only 3 years after the discovery of the antipsychotic action of chlorpromazine and 1 or 2 years after the rediscovery of the anti-- psychotic action of reserpine (reported by Indian psychiatrists three decades earlier). At this stage, I was introduced by Brodie and his collaborator, Parkhurst Shore, to the most modern methods of biochemical pharmacology available at that time, as well as into the hottest area of neuropsychopharmacology.
Brodie's background was in organic chemistry, but he had specialized in drug metabolism, which he had pioneered by developing a multitude of methods for measuring the levels of drugs and their metabolites in tissues and body fluids. At the time of my visit the prototype of a new instrument, the spectrophotofluorimeter had been constructed in Brodie's laboratory by Robert Bowman in collaboration with Sidney Udenfriend. This instrument was to revolutionize the measurement not only of drugs but also of several endogenous compounds of great physiological interest. It combined a high sensitivity with specificity. For several decades this instrument dominated biochemical pharmacology, but has now been surpassed by even more sophisticated equipment.
The antipsychotic actions of chlorpromazine and reserpine, and the finding that D-lysergic acid diethylamide (LSD) seemed to possess affinity for serotonin receptors, inspired Brodie...