Introduction to the Pharmacology of Central Nervous System (CNS) Drugs

Introduction to  the Pharmacology of Central Nervous System (CNS) Drugs

Drugs acting in the central nervous system (CNS) were among the first to be discovered by primitive humans and are still the most widely used group of pharmacologic agents. In addition to their use in therapy, many drugs acting on the CNS are used without prescription to increase the sense of well-being.

The mechanisms by which various drugs act in the CNS have not always been clearly understood. In recent decades, however, dramatic advances have been made in the methodology of CNS pharmacology. It is now possible to study the action of a drug on individual cells and even single ion channels within synapses. The information obtained from such studies is the basis for several major developments in studies of the CNS.

First, it is clear that nearly all drugs with CNS effects act on specific receptors that modulate synaptic transmission. A very few agents such as general anesthetics and alcohol may have nonspe-cific actions on membranes (although these exceptions are not fully accepted), but even these non–receptor-mediated actions result in demonstrable alterations in synaptic transmission.

Second, drugs are among the most important tools for studying all aspects of CNS physiology, from the mechanism of convul-sions to the laying down of long-term memory. As described below, agonists that mimic natural transmitters (and in many cases are more selective than the endogenous substances) and antagonist are extremely useful in such studies. The Box, Natural Toxins: Tools for Characterizing Ion Channels, describes a few of these substances.

Third, unraveling the actions of drugs with known clinical efficacy has led to some of the most fruitful hypotheses regarding the mechanisms of disease. For example, information about the action of antipsychotic drugs on dopamine receptors has provided the basis for important hypotheses regarding the pathophysiology of schizophrenia. Studies of the effects of a variety of agonists and antagonists on γ-aminobutyric acid (GABA) receptors have resulted in new concepts pertaining to the pathophysiology of several diseases, including anxiety and epilepsy.