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  • Updated 03.17.2021
  • Released 02.09.1999
  • Expires For CME 03.17.2024




This article starts with a history of the development of neuropharmacology in the past century, which began with 4 drugs and now includes more than 100 approved drugs available to a neurologist in clinical practice. The author reviews the molecular basis of neuropharmacology with a focus on clinical applications. Mode of action of drugs is explained as drug receptor interaction. Brain imaging, both PET and fMRI, are now being used for study of drug action on the brain in vivo. Therapeutic drug monitoring is important as a guide to maintenance of proper doses and blood levels of some CNS drugs. New technologies such as nanobiotechnology are being applied to the development of neurotherapeutics. As the pathomechanisms of neurologic disorders becomes better understood, the focus is on development of neuroprotective rather than symptomatic treatments, particularly for neurodegenerative disorders, stroke, and CNS trauma.

Key points

• Advances in molecular biology and various “-omics” such as genomics and proteomics have led to the development of molecular neuropharmacology.

• Several new drugs are being discovered and developed for the treatment of neurologic disorders.

• The delivery of drugs to the central nervous system and drug safety are still important issues that require attention.

• The practice of personalized neurology will require matching the most suitable drugs to individual patients.

Historical note and terminology

Neuropharmacology as a branch of pharmacology evolved slowly during the past 50 years with the introduction of drugs for neurologic disorders. Only 4 drugs for the treatment of neurologic disorders existed prior to 1900: morphine for pain, caffeine for drowsiness, nitrous oxide anesthesia for surgery, and aspirin for pain. Four more drugs were introduced between 1900 and 1950: barbiturates and phenytoin for epilepsy, meperidine and analogs for pain, and antihistaminics for wakefulness. Discoveries in the neurosciences that have helped to build the foundations for neuropharmacology are shown in Table 1.

Table 1. Landmarks in the Development of Neuropharmacology


Events and author

1890 to 1910

Introduction of the term "synapse" by Sherrington and Cajal for the site of interaction among neurons, between neurons and effectors.

1920 to 1950

Scientific basis of pharmacology. Identification of acetylcholine and norepinephrine as peripheral nervous system transmitters. Discovery of serotonin in blood (36). Drug receptor interactions were approached in a quantitative manner.

1950 to 1980

Beginning of chemical neuroanatomy and neuropharmacology. Discovery of major CNS neurotransmitters and their mechanisms. GABA recognized as a principal neuroinhibitory neurotransmitter. Identification of serotonin in the brain and proposal of its role as a neurotransmitter (02). The first ion channels, sodium and potassium, were discovered (19). Topographical mapping with EEG was used in neuropharmacology to assess the effects of nootropic (Greek noos for “mind” and tropos for "turn forward") medications. This term is used for medications that enhance the cognitive function (33).

1980 to 1990

Role of amino acids and peptides became prominent. Characterization of receptors by ligand binding studies.

1990 to 1999

Decade of the Brain. Molecular biology impacts neuropharmacology to start the era of molecular neuropharmacology. Cloning of receptors. Parallel advances in pharmacogenetics and pharmacogenomics with genome mapping. Gene therapy of neurologic disorders in experimental stage.

2000 to present

Start of the post-genomic era. New drug discovery and development based on genomic and proteomic technologies. Development of personalized medicines for neurologic disorders (26). Introduction of cell- and gene-based medicines in development for neurologic disorders. Emphasis on disease modification and neuroprotection rather than symptomatic treatment (24).

The idea that drugs might act by binding to a receptor in the cell existed in the early part of the 20th century, but identification of the receptors did not start until 1980. The pace of defining the nature of the sites of action of drugs accelerated during the 1980s and 1990s due to advances in molecular biology. The primary amino acid sequence of many receptors was determined from the nucleic acid sequence of their cDNAs. Molecular targets of drugs acting on the central nervous system were defined, and one can refer to this area of study as molecular pharmacology. Increasing molecular understanding of the receptors has enabled improved drug design. Whereas organic chemistry provided the background for synthesis of new drugs in the past, current advances in genomic and proteomic technologies are now revolutionizing the drug discovery and development process.

Since the 1950s, the number of drugs used for neurologic disorders has steadily increased. Currently, there are over 100 drugs in use for neurologic disorders and over 500 drugs for neurologic disorders that are in development by the pharmaceutical industry.

Principles of general pharmacology are applied to the study of neuropharmacology when it involves drugs administered systemically. Exceptions are special procedures for delivering drugs directly to targets in the central nervous system. Similar principles apply to gene therapy of neurologic disorders, except when drugs such as antisense oligodeoxynucleotides are administered systemically for blocking the production of disease-causing proteins by interfering with either the transcription of DNA to mRNA, or the translation of mRNA to proteins. A refinement of antisense approach is RNA interference for gene silencing in which small interfering RNAs or siRNAs are used in a sequence-specific manner to recognize and destroy complementary RNAs.

This article will describe aspects of neuropharmacology that are of interest to practicing neurologists.

Basic terms that are used in the discussion of the pharmacology of drugs acting on the nervous system are:

Pharmacodynamics. This is the fundamental action of a drug on a physiological, biochemical, or molecular level. The term “neuropharmacodynamics” is used for action of drugs on the central nervous system.

Pharmacokinetics. This term is applied to drug concentrations in body fluids and tissues as well as its metabolism during the passage through the body. It also covers the influence of various factors on these processes. Neuropharmacokinetics refers to penetration, distribution, and excretion of drugs introduced into the central nervous system.

Drug receptors. Specific macromolecules, peptides, proteins, enzymes, nucleic acids, ion channels, etc., where the initial molecular event occurs on introduction of the drug into the body. Proteins and enzymes constitute most of the sites of drug action. When a therapeutic response follows, this is referred to as "site of action" of the drug.

Pharmacogenetics. A term applied to the influence of genetic factors on the action of drugs, ie, which drugs work best on which patients and the genetic basis of susceptibility to adverse reactions of drugs.

Pharmacogenomics. An offshoot of genomics that usually refers to the application of genomic technologies to drug discovery and development. Pharmacogenomics now seeks to examine the way drugs act on the cells as revealed by the gene expression patterns, thus, bridging the fields of medicinal chemistry and genomics. Discovery of gene polymorphisms by genomic technologies contributes to the development of personalized medicines that work best in certain individuals.

Pharmacoproteomics. This is the application of proteomics to drug discovery and development. Subtyping of patients based on protein analysis may help to match a particular target-based therapy to a particular biomarker in a subgroup of patients. The use of proteomic strategies is having a significant impact on the development of neuropharmacology.

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