ABSTRACT
Central nervous system Many drugs (Table 5.1) have both intentional and unintended central nervous system (CNS) pharmacologic effects (see Table 5.2 for examples).
One characteristic that distinguishes CNS safety pharmacology from discovery or ef˜cacy pharmacology (primary pharmacology) is that CNS safety pharmacology is generally conducted in normal animals. The aim is to see whether the new drug induces adverse changes in normal function, and not whether the drug can have potential therapeutic effects on abnormal function. Not to be included in CNS safety pharmacology studies therefore would be models of pathology or disease (e.g., depression, anxiety), unless it was expected that the therapeutic use of the drug might present particular problems in a speci˜c group of patients. Indeed, the notion of safety might differ radically depending on the intended therapeutic application. For example, when developing an N-methyl-D-aspartic acid (NMDA) antagonist for acute stroke, it would not be a very important safety factor if the drug induced a reversible psychotomimetic state, providing the patient’s life was saved. On the other hand, if such a drug were to be used preventively in patients suffering repeated minor strokes, the presence or absence of psychotomimetic potential could become a crucial safety consideration.
