DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Neurotransmission and the
Central Nervous System
Perry B. Molinoff
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 to 17, 21, 22, and 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 basic intracortical processing module of ~100 vertically
connected cortical columns (Mountcastle, 1997). Varying numbers
of adjacent columnar modules may be functionally linked into
larger information- processing ensembles. The pathology of
Alzheimer’s disease, e.g., destroys the integrity of the columnar
modules and the corticocortical connections (Chapter 22). Cortical
areas termed association areas process information from primary
cortical sensory regions to produce higher cortical functions such as
abstract thought, memory, and consciousness. The cerebral cortices
also provide supervisory integration of the autonomic nervous