CHAPTER 5

ANTIPSYCHOTIC AGENTS

Conventional antipsychotics
What makes an antipsychotic “conventional”?
In this section we will discuss the pharmacologic properties of the first drugs that were
proven to effectively treat schizophrenia. A list of many conventional antipsychotic drugs is
given in Table 5-1. These drugs are usually called conventional antipsychotics, but they are
sometimes also called classical antipsychotics, or typical antipsychotics, or first-generation
antipsychotics. The earliest effective treatments for schizophrenia and other psychotic illnesses
arose from serendipitous clinical observations more than 60 years ago, rather than from scientific
knowledge of the neurobiological basis of psychosis, or of the mechanism of action of effective
antipsychotic agents. Thus, the first antipsychotic drugs were discovered by accident in the
1950s when a drug with antihistamine properties (chlorpromazine) was serendipitously observed
to have antipsychotic effects when this putative antihistamine was tested in schizophrenia
patients. Chlorpromazine indeed has antihistaminic activity, but its therapeutic actions in
schizophrenia are not mediated by this property. Once chlorpromazine was observed to be an
effective antipsychotic agent, it was tested experimentally to uncover its mechanism of
antipsychotic action. Early in the testing process, chlorpromazine and other antipsychotic agents
were all found to cause “neurolepsis,” known as an extreme form of slowness or absence of
motor movements as well as behavioral indifference in experimental animals. The original
antipsychotics were first discovered largely by their ability to produce this effect in experimental
animals, and are thus sometimes called “neuroleptics.” A human counterpart of neurolepsis is
also caused by these original (i.e., conventional) antipsychotic drugs and is characterized by
psychomotor slowing, emotional quieting, and affective indifference.