Psychoactive Drugs Chemotherapy of the Mind

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It is difficult to exaggerate the complexity of the human brain's chemistry and functions, many of which are only beginning to be understood. Much is still undiscovered.

Before embarking on a discussion of mental diseases and mechanistic aspects of the drugs used in their treatment, it is important to define certain terms frequently encountered.

Psychosis. A mental disorder of sufficient magnitude to result in personality breakdown and loss of contact with reality. Delusions and hallucinations are characteristic. Institutionalization is invariably necessary. There are several types of psychoses.

Depressive. Characterized by extreme depression and melancholia.

Involutional. Usually occurring during involutional period of a person's physical decline (age 45-65).

Manic-depressive. Characterized by alternating periods of severe depression and excessive well-being; sometimes even alternating with periods of apparent normalcy.

Senile. "Caused" by old age.

Toxic. Caused by a toxic agent.

Traumatic. Resulting from head injuries.

Neurosis. A mental disorder that is not caused by demonstrable disease of any part in the central nervous system. Life adjustments are impaired, but contact with reality is not lost. Treatment does not require hospitalization but it is complicated in that patients usually have mixed psychoneuroses of two or more of the following types: fatigue, anxiety, phobic, hysterical, obsessive-compulsive, hypochondriasis, and others.

Psychotropic agent. A chemical that affects psychic functions and behavior. This would include drugs used to treat mental disorders, as well as drugs that may cause them (e.g., hallucinogens).

Schizophrenia. A group of severe mental disorders involving disturbances of thinking, mood, and behavior, including delusions and hallucinations. Four main types are usually considered.

Simple. Characterized by emotional dullness, loss of ambition, and withdrawal tendency.

Paranoid. Characterized by delusions of persecution.

Catatonic. Marked by excitement or stupor, yet lucidity ; exhibits so-called split personality.

Hebephrenic. Marked by speech anomalies, silly childish behavior, delusions, and hallucinations.

Tranquilizer. A drug capable of reducing mental tension without interfering with normal function.

Ataractic. A drug producing ataraxia, which is a state of mental calm and tranquility.

Neuroleptic. A drug producing symptoms similar to those of depressant diseases of the central nervous system (CNS). Frequently used to refer to an antipsychotic agent.

Thymoleptic. A synonym for an antidepressant drug.

It is difficult to find a widely acceptable system of classification of psychotropic agents. One classification that is useful is the following:

I. General Sedatives

A. Sedatives

B. Hypnotic

C. Narcotics

II. Tranquilizers

A. Minor

1. Carbamates

2. Benzodiazepines

3. Diphenylmethanes

B. Major

1. Phenothiazines

2. Reserpines

3. Butyrophenones

4. Miscellaneous agents

III. Antidepressants

A. Tricyclics

B. MAO inhibitors

C. Others

IV. Psychotostimulant

A. Psychotoanaleptics (amphetamines)

B. Psychotodyleptics (hallucinogens)

Some of this classification is not "pure" in that agents in some subcategories have multiple pharmacological properties that are frequently of clinical usefulness and not necessarily related to psychotropic effects. For example, some of the minor tranquilizers include members that have excellent skeletal muscle relaxant properties; several are used as antiepileptics (e.g., diazepam). The diphenylmethane derivative hydroxyzine is a particularly good example of multiple pharmacology. In addition to its anxiolytic (antianxiety) property, it also exhibits the following clinically significant assets: antihistaminic, adrenolytic, antiemetic, antispasmodic, hypothermic, and sedative effects.

12.1. Historical Overview

Humanity's first "mood-altering" substances were herbal sedatives and alcohol. Plants, which are now known to contain opium and belladonna alkaloids, were discovered millennia ago but entered "mainstream" medicine during the Renaissance and were widespread by the eighteenth century. The nineteenth century saw the introduction of inorganic bromides as antiepileptics in 1853 and as sedatives in 1864. The chemical "chloral," which was discovered by Liebig in 1832, entered medical practice after 1869 as chloral hydrate (Eq. 12.1). Paraldehyde, which is a trimer of acetaldehyde, came into use about a decade later. The long-acting barbiturate barbital was developed in 1903, followed by phénobarbital in 1912. The middle 1930s saw the introduction of short-acting barbiturates such as seco- and pentobarbital. Over the years probably hundreds of barbiturates with varying durations of action were developed, and many were introduced. Many of these, in less than hypnotic doses, became popular as daytime sedatives to treat anxieties and neuroses (the term tranquilizer was not yet in use). Sulfonal and related sulfones developed in the late nineteenth century were powerful hypnotics whose toxicities caused their discontinuation some years later.

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