Modulators of nicotinic acetylcholine receptors as analgesics

Curr Opin Investig Drugs. 2004 Jan;5(1):76-81.


The analgesic properties of nicotine have prompted attempts to develop compounds that specifically target nicotinic acetylcholine receptors (nAChRs) in the nervous system, with the beneficial effects of nicotine but without its side effects. Thus far, only nAChR agonists have been reported as being in development for pain, although nAChR antagonists could also have a potentially analgesic action. Various problems associated with the use of nAChR agonists as analgesics have been identified and measures suggested to overcome some of them. This review describes the nAChR agonists A-85380, tebanicline, ABT-366833, ABT-202, ABT-894, epibatidine analogs and SIB-1663, of which ABT-366833, ABT-202 and ABT-894 are currently undergoing development as pain therapeutics. In vivo studies of the pathomechanism of neuropathic pain indicate that targeting alpha3beta4 does not have a specific action on neuropathic pain, and that alpha3beta4 ligands cause side effects. On the other hand, alpha4beta2 receptors are specific for neuropathic pain, and ligands that bind preferentially to these receptors both effectively relieve pain and do not cause many adverse effects. This is the basis of the difference between the action of tebanicline, which binds with greater specificity to alpha3beta4 receptors, and ABT-366833, which binds more specifically to alpha4beta2 receptors.

Publication types

  • Review

MeSH terms

  • Analgesics / chemistry
  • Analgesics / pharmacology*
  • Analgesics / therapeutic use
  • Animals
  • Drug Design
  • Humans
  • Nicotinic Agonists / chemistry
  • Nicotinic Agonists / pharmacology*
  • Nicotinic Agonists / therapeutic use
  • Pain / drug therapy
  • Pain / metabolism
  • Peripheral Nervous System Diseases / drug therapy
  • Peripheral Nervous System Diseases / metabolism
  • Receptors, Nicotinic / drug effects*
  • Receptors, Nicotinic / metabolism
  • Structure-Activity Relationship


  • Analgesics
  • Nicotinic Agonists
  • Receptors, Nicotinic