PAC 610 Module 1 Neurons, Neurotransmitters and History Example

Built by Accident: How Neurons Signal and How Psychiatry Found Its First Medications

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Psychology and Addiction Studies Program, Aspen University

PAC 610: Psychopharmacology

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Month Day, Year

Built by Accident: How Neurons Signal and How Psychiatry Found Its First Medications

Tasha, a counselor at Ridgeview Recovery Center, an outpatient program in Knoxville, Tennessee, invented for this paper along with its staff and clients, was meeting with a client recently diagnosed with depression alongside an alcohol use disorder. The program's psychiatric nurse practitioner had suggested an antidepressant. The client refused: "It's a chemical that numbs you. I've had enough chemicals." Tasha does not prescribe and would not try to change the decision for him. But she wanted to answer honestly when he asked her what the pills actually do. This paper builds that answer from the ground up: how nerve cells signal, which chemical messengers medications act on and how psychiatry came to have medications at all.

How a Signal Crosses the Gap

A neuron receives signals through its branching dendrites and cell body. When enough excitatory input arrives, the cell fires an action potential, a brief electrical change that travels down the axon to its terminals. There, the signal cannot jump to the next cell, because a tiny gap, the synapse, separates them. Instead, the arriving impulse causes small sacs called vesicles to release a chemical messenger, a neurotransmitter, into the gap. The neurotransmitter crosses and binds to receptors on the receiving cell, much as a key fits a lock. Depending on the receptor, binding makes the receiving cell more or less likely to fire.

The signal must also stop. Some neurotransmitters are broken down by enzymes in the gap or inside the cell. Many are pulled back into the sending neuron by transporter proteins, a process called reuptake, to be reused. This cleanup is where many psychiatric medications act. A drug can block reuptake, leaving more of the messenger in the gap for longer; block a receptor, so the messenger cannot act; stimulate a receptor, imitating the messenger; or block an enzyme that breaks the messenger down.

Five Messengers

An Anesthetic Becomes an Antipsychotic

Shen (1999) traced the history of antipsychotic drugs to a French surgeon, Henri Laborit, who in the early 1950s was looking for ways to reduce surgical shock. He noticed that the compound chlorpromazine left patients calm and indifferent to their surroundings without putting them to sleep. He suggested that psychiatrists try it, and in 1952 Jean Delay and Pierre Deniker reported that it reduced agitation and psychotic symptoms in hospitalized patients. Within a few years, chlorpromazine was used worldwide, and hospital populations began to change. Shen describes how this was followed by haloperidol later in the decade and, much later, by clozapine and the newer antipsychotics. The mechanism, blocking dopamine receptors, was worked out only after the drugs were in use.

A Failed Antipsychotic Becomes an Antidepressant

The first tricyclic antidepressant came from an attempt to find a better antipsychotic. Kuhn (1958), a Swiss psychiatrist, tested a compound chemically similar to chlorpromazine, known then as G 22355, in his hospital patients. It did little for psychosis. But Kuhn observed that patients with severe depression improved: they became more active, their mood lifted and the slowed thinking and movement typical of their illness eased, often after several days to weeks of treatment. He reported the results in the American Journal of Psychiatry as the treatment of depressive states with imipramine, noting both the benefits and the side effects.

Lopez-Munoz and Alamo (2009) describe how a parallel accident occurred with iproniazid, a tuberculosis drug that seemed to lift patients' mood and was later shown to block monoamine oxidase, an enzyme that breaks down monoamine neurotransmitters. Once researchers learned that imipramine blocked the reuptake of norepinephrine and serotonin and that iproniazid prevented their breakdown, a theory took shape: depression might reflect too little monoamine activity, and antidepressants might work by increasing it. This monoamine theory guided the search for new drugs for decades and led, through deliberate design rather than chance, to the selective serotonin reuptake inhibitors.

What the Monoamine Theory Got Wrong

Lopez-Munoz and Alamo also note the theory's limits. Antidepressants change neurotransmitter levels within hours, yet improvement usually takes weeks, which suggests that the benefit depends on slower changes in the brain that follow, not on the chemical increase itself. Not everyone with depression responds, and some respond to drugs that act on quite different systems. The theory was a useful starting point that has given way to more complex accounts involving receptor changes, stress systems and the growth of new connections between neurons. The popular phrase "chemical imbalance" oversimplifies even the original theory.

What This Means for the Conversation

The history gives Tasha something more honest to offer her client than reassurance. She can explain that an antidepressant does not add a foreign chemical that numbs feeling; it changes how long the brain's own messengers stay active, and its benefits seem to come from changes that develop over weeks. She can say that these medications were discovered partly by careful observation of patients, that they help many people and not everyone and that the prescriber is the right person to discuss whether one fits him. She can also acknowledge his reason for caution: someone who has used alcohol to change how he feels has good cause to be wary of anything else that does, and that wariness deserves a real conversation with the nurse practitioner rather than a sales pitch.

Conclusion

Psychiatric medications act at the synapse, changing how long and how strongly the brain's own messengers work, most often by blocking reuptake, blocking or stimulating receptors or slowing breakdown. The field began with accidents observed by careful clinicians: an anesthetic that calmed, a failed antipsychotic that lifted depression. The theories built afterward were useful and incomplete. A counselor who understands both the mechanism and the history can explain medication to clients plainly and honestly, without overstating what is known.

References

Kuhn, R. (1958). The treatment of depressive states with G 22355 (imipramine hydrochloride). American Journal of Psychiatry, 115(5), 459-464. https://doi.org/10.1176/ajp.115.5.459

Lopez-Munoz, F., & Alamo, C. (2009). Monoaminergic neurotransmission: The history of the discovery of antidepressants from 1950s until today. Current Pharmaceutical Design, 15(14), 1563-1586. https://doi.org/10.2174/138161209788168001

Shen, W. W. (1999). A history of antipsychotic drug development. Comprehensive Psychiatry, 40(6), 407-414. https://doi.org/10.1016/S0010-440X(99)90082-2