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SECTION V DRUGS THAT ACT IN THE CENTRAL

NERVOUS SYSTEM

C H A P T E R

Introduction to the 21

Pharmacology of

CNS Drugs

*
John A. Gray, MD, PhD

Drugs acting in the central nervous system (CNS) were among fully accepted), even these non–receptor-mediated actions result
the first to be discovered by primitive humans and are still the in demonstrable alterations in synaptic transmission.
most widely used group of pharmacologic agents. These include Second, drugs are among the most valuable tools for studying
medications used to treat a wide range of neurologic and psychi- CNS function, from understanding the mechanism of convul-
atric conditions as well as drugs that relieve pain, suppress nausea, sions to the laying down of long-term memory. Both agonists that
and reduce fever, among other symptoms. In addition, many mimic natural transmitters (and in many cases are more selective
CNS-acting drugs are used without prescription to increase the than the endogenous substances) and antagonists are extremely
sense of well-being. useful in such studies. Third, unraveling the actions of drugs
Due to their complexity, the mechanisms by which various with known clinical efficacy has led to some of the most fruitful
drugs act in the CNS have not always been clearly understood. hypotheses regarding the mechanisms of disease. For example,
In recent decades, however, dramatic advances have been made information about the action of antipsychotic drugs on dopamine
in the methodology of CNS pharmacology. It is now possible to receptors has provided the basis for important hypotheses regard-
study the action of a drug on individual neurons and even single ing the pathophysiology of schizophrenia. Studies of the effects
receptors within synapses. The information obtained from such of a variety of agonists and antagonists on γ-aminobutyric acid
studies is the basis for several major developments in studies of the (GABA) receptors have resulted in new concepts pertaining to
CNS. First, it is clear that nearly all drugs with CNS effects act the pathophysiology of several diseases, including anxiety and
on specific receptors that modulate synaptic transmission. While a epilepsy.
few agents such as general anesthetics and alcohol may have non- A full appreciation of the effects of a drug on the CNS requires
specific actions on membranes (although these exceptions are not an understanding of the multiple levels of brain organization,
from genes to circuits to behavior. This chapter provides an intro-
duction to the functional organization of the CNS and its synaptic
* transmitters as a basis for understanding the actions of the drugs
The author thanks Dr. Roger A. Nicoll for his contributions to previous
editions. described in the following chapters.
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