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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Competitive Neuronal Nicotinic Receptor Antagonists: A New Direction for Drug Discovery

Linda P. Dwoskin and Peter A. Crooks
Journal of Pharmacology and Experimental Therapeutics August 2001, 298 (2) 395-402;
Linda P. Dwoskin
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Peter A. Crooks
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Abstract

Neuronal nicotinic acetylcholine receptors are distributed extensively throughout the central and peripheral nervous systems. Currently, there is great interest in determining the structural and functional diversity of these receptors, and in developing subtype-selective agonists that have potential as therapeutic agents for neuropathology and disease. However, relatively little attention has been focused on the development of subtype-selective nicotinic receptor antagonists. Such antagonists would be beneficial for establishing the role of specific nicotinic receptor subtypes in physiological function and for unraveling the complexities of neuronal nicotinic receptor function. Furthermore, these subtype-selective antagonists may also prove to be beneficial in the treatment of neuropathology and disease. The current perspective summarizes the research that has been carried out with both classical competitive antagonists and more recently developed competitive nicotinic receptor antagonists.

Footnotes

  • This work was supported in part by Grants DA00399, DA10934, and DA13519 from the National Institutes of Health.

  • Abbreviations:
    nAChRs
    neuronal nicotinic acetylcholine receptors
    CNS
    central nervous system
    αBTX
    α-bungarotoxin
    ACh
    acetylcholine
    SARs
    structure-activity relationships
    DHβE
    dihydro-β-erythroidine
    DA
    dopamine
    MLA
    methyllycaconitine
    nBTX
    n-bungarotoxin
    NDNI
    N-n-decylnicotinium
    NDDNI
    N-n-dodecylnicotinium
    NNNI
    N-n-nonylnicotinium
    NONI
    N-n-octylnicotinium
    α3β2*
    * indicates putative receptor subtype assignment
    • Received January 26, 2001.
    • Accepted April 3, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 298 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 298, Issue 2
1 Aug 2001
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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Competitive Neuronal Nicotinic Receptor Antagonists: A New Direction for Drug Discovery

Linda P. Dwoskin and Peter A. Crooks
Journal of Pharmacology and Experimental Therapeutics August 1, 2001, 298 (2) 395-402;

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Research ArticlePERSPECTIVES IN PHARMACOLOGY

Competitive Neuronal Nicotinic Receptor Antagonists: A New Direction for Drug Discovery

Linda P. Dwoskin and Peter A. Crooks
Journal of Pharmacology and Experimental Therapeutics August 1, 2001, 298 (2) 395-402;
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