Nicotinic acetylcholine receptors: an overview on drug discovery

Expert Opin Ther Targets. 2009 Apr;13(4):395-411. doi: 10.1517/14728220902841045.

Abstract

Background: Nicotinic acetylcholine receptors (nAChRs) are ligand-gated ion channels that participate in many physiological functions. Receptors result from the assembly of five homologous or heterologous subunits that form the ligand-binding site and an ionic pore. In vertebrates, 17 subunits have been identified, alpha (1 - 10), beta (1 - 4), gamma, delta and epsilon. Assembly of different subunit combinations allows a diversity of physiological and pharmacological properties.

Objective: To review the putative involvement of nAChRs in several diseases.

Methods: We discuss the expression pattern of the subunits, the pharmacological tools for distinguishing them and their role in pathogenesis.

Results/conclusion: Long-standing efforts in this field should soon result in the finding of new molecules that might be applicable to situations ranging from neurological diseases to immune treatments.

Publication types

  • Review

MeSH terms

  • Allosteric Regulation / drug effects
  • Analgesics / pharmacology
  • Analgesics / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / etiology
  • Drug Discovery
  • Hearing / physiology
  • Humans
  • Myasthenia Gravis / etiology
  • Myasthenia Gravis / immunology
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / physiopathology
  • Neurodegenerative Diseases / prevention & control
  • Nicotine / adverse effects
  • Nicotine / pharmacology
  • Nicotine / therapeutic use
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Agonists / therapeutic use
  • Nicotinic Antagonists / pharmacology*
  • Nicotinic Antagonists / therapeutic use
  • Pain / drug therapy
  • Pain / physiopathology
  • Protein Subunits / drug effects
  • Psoriasis / etiology
  • Pyridines / adverse effects
  • Pyridines / pharmacology
  • Pyridines / therapeutic use
  • Receptors, Nicotinic / classification
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / immunology
  • Receptors, Nicotinic / physiology
  • Schizophrenia / drug therapy
  • Schizophrenia / etiology
  • Schizophrenia / physiopathology
  • Smoking / adverse effects
  • Smoking Cessation
  • Tobacco Use Disorder / drug therapy
  • Tobacco Use Disorder / physiopathology

Substances

  • Analgesics
  • Bridged Bicyclo Compounds, Heterocyclic
  • Nicotinic Agonists
  • Nicotinic Antagonists
  • Protein Subunits
  • Pyridines
  • Receptors, Nicotinic
  • Nicotine
  • epibatidine