The therapeutic potential of nicotinic acetylcholine receptor agonists for pain control

Expert Opin Investig Drugs. 2001 Oct;10(10):1819-30. doi: 10.1517/13543784.10.10.1819.


Due to the limitations of currently available analgesics, a number of novel alternatives are currently under investigation, including neuronal nicotinic acetylcholine receptor (nAChR) agonists. During the 1990s, the discovery of the antinociceptive properties of the potent nAChR agonist epibatidine in rodents sparked interest in the analgesic potential of this class of compounds. Although epibatidine also has several mechanism-related toxicities, the identification of considerable nAChR diversity suggested that the toxicities and therapeutic actions of the compound might be mediated by distinct receptor subtypes. Consistent with this view, a number of novel nAChR agonists with antinociceptive activity and improved safety profiles in preclinical models have now been identified, including A-85380, ABT-594, DBO-83, SIB-1663 and RJR-2403. Of these, ABT-594 is the most advanced and is currently in Phase II clinical evaluation. Nicotinically-mediated antinociception has been demonstrated in a variety of rodent pain models and is likely mediated by the activation of descending inhibitory pathways originating in the brainstem with the predominant high-affinity nicotine site in brain, the alpha4beta2 subtype, playing a critical role. Thus, preclinical findings suggest that nAChR agonists have the potential to be highly efficacious treatments in a variety of pain states. However, clinical proof-of-principle studies will be required to determine if nAChR agonists are active in pathological pain.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Nicotinic Agonists / adverse effects
  • Nicotinic Agonists / pharmacokinetics
  • Nicotinic Agonists / pharmacology
  • Nicotinic Agonists / therapeutic use*
  • Pain / drug therapy*
  • Pain Measurement / drug effects
  • Receptors, Nicotinic / drug effects*


  • Nicotinic Agonists
  • Receptors, Nicotinic