Chapter 14

### INTRODUCTION

Drugs that act in the central nervous system (CNS) are invaluable therapeutically. They can, e.g., relieve pain, reduce fever, suppress disordered movements, induce sleep or arousal, reduce appetite, and allay the tendency to vomit. Selectively acting drugs can be used to treat anxiety, depression, mania, or schizophrenia and do so without altering consciousness (Chapters 15 and 16). Socially acceptable stimulants and anti-anxiety agents contribute to emotional stability, relief of anxiety, and pleasure. However, the excessive use of such drugs can affect lives adversely when uncontrolled, self-administration leads to physical dependence or to toxic side effects (Chapter 24). The nonmedical self-administration of CNS-active drugs— recreational pharmacology—is widespread.

The identification of targets for drugs that affect the nervous system and behavior presents extraordinary scientific challenges. Understanding the cellular and molecular basis for the complex and varied functions of the human brain is only the beginning. Complicating the effort is the fact that a CNS-active drug may act at multiple sites with disparate and even opposing effects. In addition, many CNS disorders involve multiple brain regions and pathways, which can frustrate efforts to use a single therapeutic agent. CNS pharmacologists have two overlapping goals: to use drugs to elucidate the mechanisms that operate in the normal CNS, and to develop drugs to correct pathophysiological events in the abnormal CNS. Advances in molecular biology and neurobiology are facilitating the development of drugs that can selectively treat diseases of the CNS.

This chapter introduces guidelines and fundamental principles for the comprehensive study of drugs that affect the CNS. Specific therapeutic approaches to neurological and psychiatric disorders are discussed in Chapters 15, 16, 17, 21, 22, 24. For further detail, see the specialized texts by Cooper (2003), Siegel (2006), Nestler (2009), and their associates. For detailed information on specific receptors and ion channels see the official database of the IUPHAR Committee on Receptor Nomenclature and Drug Classification.

### ORGANIZATIONAL PRINCIPLES OF THE CNS

The brain is a complex assembly of interacting neurons and nuclei that regulate their own and each other's activities in a dynamic fashion, generally through chemical neurotransmission. It is useful to examine the major anatomical regions of the CNS and their associations with specific neurotransmitter systems and the effect of pharmacological agents thereon.

Cerebral Cortex. The two cerebral hemispheres constitute the largest division of the brain. Regions of the cortex are classified in several ways:

• by the modality of information processed (e.g., sensory, including somatosensory, visual, auditory, and olfactory, as well as motor and associational)

• by anatomical position (frontal, temporal, parietal, and occipital)

• by the geometric relationship between cell types in the major cortical layers ("cytoarchitectonic" classification)

The specialized functions of a cortical region arise from the interplay between connections with other regions of the cortex (corticocortical systems) and noncortical areas of the brain (subcortical systems) and a ...

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