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KEY CONCEPTS

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  • An understanding of drug action in the brain must integrate knowledge of the molecular and cellular actions of a drug with their effects on brain circuitry.

  • The clinical actions of a drug in the brain often are due to neural plasticity—the long-term adaptations of neurons to the sustained short-term actions of a drug.

  • The binding of a drug to its specific target(s) normally is saturable and stereoselective.

  • The specific binding of a drug to its target is quantified according to its affinity for the target, expressed as a dissociation constant (Kd), and the total amount of binding (Bmax).

  • Potency of a drug describes the strength of binding between the drug and its target; efficacy describes the maximal biologic effects that the drug exerts by binding to its target.

  • Drugs can be classified as agonists, partial agonists, inverse agonists, partial inverse agonists, or antagonists.

  • Modern neuropharmacology takes advantage of the tools of molecular biology, genetics, and cell biology as well as combinatorial chemistry, which is used to generate novel molecules that may function as new drugs.

  • Functional genomics and proteomics will help identify novel drug targets.

  • Pharmacogenetics will guide the choice of drug treatments based on an individual’s genetic constitution.

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INTRODUCTION

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Neuropharmacology is the scientific study of the effects of drugs on the nervous system. Its primary focus is the actions of medications for psychiatric and neurologic disorders as well as those of drugs of abuse. Neuropharmacology also uses drugs as tools to form a better understanding of normal nervous system functioning. The goal of neuropharmacology is to apply information about drugs and their mechanisms of action to develop safer, more effective treatments and eventually curative and preventive measures for a host of nervous system abnormalities. The importance of neuropharmacology to medical practice, and to society at large, is difficult to overstate. Drugs that act on the nervous system, including antidepressant, antianxiety, anticonvulsant, and antipsychotic agents, are among the most widely prescribed medications. Moreover, commonly prescribed medications that act on other organ systems often are associated with side effects that involve the nervous system and in turn may limit their clinical utility. In addition, a substantial number of individuals use common substances, such as caffeine, alcohol, and nicotine, that are included in the domain of neuropharmacology because of their effects on the central nervous system (CNS). In a much smaller fraction of the population, these and other drugs are used compulsively, in a manner that constitutes an addiction. Drug abuse and addiction exact an astoundingly high financial and human toll on society through direct adverse effects, such as lung cancer and hepatic cirrhosis, and indirect adverse effects—for example, accidents and AIDS—on health and productivity. Still other common afflictions of the nervous system, such as Alzheimer disease as just one example, are awaiting effective medications, further emphasizing the importance of neuropharmacology.

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Neuropsychopharmacology is an all-encompassing term that ...

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