California Association of Chemistry Teachers
Walter J. Moore and Henry R. Mahler
Indiana university Bloomingfon
Introduction to Molecular P~y~hoIogy
W e are today close to a critical point in history a t which the mind of man by taking thought (and making experiments)will be able to understand the chemical and physical mechanisms responsible for thought itself. Just as molecular biology has provided a chemical basis for heredity and evolution, molecular psychology will elucidate the chemistry of memory, learning, sensation, emotion, and finally human consciousness. Sherringtou warned in 1933 against easy optimism: "I reflect with apprehension that a great subject can revenge itself shrewdly for being too hastily touched." Yet advances in neurochemistry and neurophysiology during the past 30 years indicate that a t last we have a t hand the experimental and theoretical equipment needed to study the molecular basis of mental activity.
and cooperative; the milder cases can be sent home with the disease arrested. Despite an increased rate of admissions, the population of the mental hospitals is declining. I t must be clearly stated, however, that there are many cases of so-called hard core schizophrenia, which do not respond to drugs a t all.
Same Small Molecules
Ten years ago mental hospitals were in fact insane asylums. The incidence of schizophrenia was high and constantly increasing. Many of the patients were dangerous maniacs, kept in solitary confinement in concrete cells which only hardened keepers dared to enter. Others were human vegetables, hut much more nnpleasant to handle than any vegetable. The therapy of this disease, despite ornate psychoanalytic theories as to its origin, had reached a dead end. Sometimes a patient was given massive doses of barbiturates, hut when he awoke from his stupor, the madness continued as before. One day in 1952 two French physicians, Delay and Deniker (I), decided to try an antihistamine analog instead of a barbiturate, and by good chance they selected one of the phenothiazine drugs, chlorpromazine. The results were immediate and spectacular: the first real clue to a chemotherapy of schizophrenia had been discovered. Although many changes in the basic molecule (Fig. l) have been tried, the original is still important in practice. Today the mental hospital presents a changed picture. Restraint is seldom necessary. The worst cases of schizophrenia often become docile, sociable, This paper originated in a lecture given by W. J. M. s t the 1964 Spring Meeting of the California Association of Chemistry Teachers. The authors have formed a joint project for research and graduate training in brain chemistry. This project is part of a broad interdisciplinary program in Neurosciences now in progress at Indiana University.
Figure 1.
Chlorprornorine.
Schizophrenia is a disease that seems to involve the deep, old portion of the brain. This is the region that contains the primal instincts-self preservation, hunger, reproduction. These are the instincts that man shares with the earliest vertebrates, such as the reptiles. The chemical transmitters (Fig. 2) betyeen cells in most of these old parts of the brain belong to the catecholamine group-dopamine and norepinephrine. These amines, and possibly also serotonin [5-hydroxytryptaminel probably act on membranes of nerve cells to influence their permeahility to ions, particularly Na+ and I
