Partial agonists as therapeutic agents at neuronal nicotinic acetylcholine receptors
- PMID:16979139
- DOI: 10.1016/j.bcp.2006.08.010
Partial agonists as therapeutic agents at neuronal nicotinic acetylcholine receptors
Abstract
Improved understanding of how brain function is altered in neurodegenerative disease states, pain and conditions, such as schizophrenia and attention deficit disorder, has highlighted the role of nicotinic acetylcholine receptors (nAChRs) in these conditions and identified them as promising therapeutic targets. nAChRs are widely expressed throughout the peripheral and central nervous system, and this widespread nature underlines the need for new ligands with different selectivities and pharmacological profiles if we are to avoid the adverse side effects associated with many of the nAChR modulators currently identified. Partial agonists have the unique property of being able to act both as agonists or antagonists depending on the concentration of endogenous neurotransmitter. Moreover, the agonist action of partial agonists has a 'ceiling' effect, giving them a large safety margin and making them an attractive proposition for therapeutic molecules. Partial agonists of nAChRs are currently being developed as a nicotine replacement therapy for smoking cessation and for the treatment of a number of neurological diseases associated with a loss of cholinergic function. This commentary will discuss the pharmacological properties of partial agonists and review recent research developments in the field of partial agonists acting at nicotinic receptors.
Similar articles
- [Role of smoking and nicotine in neuropsychiatric disorders: evidence for therapeutic role of nicotinic acetylcholine receptors].Miyata H.Miyata H.Nihon Shinkei Seishin Yakurigaku Zasshi. 2008 Aug;28(4):149-58.Nihon Shinkei Seishin Yakurigaku Zasshi. 2008.PMID:18800618Review.Japanese.
- Modulators of nicotinic acetylcholine receptors as analgesics.Jain KK.Jain KK.Curr Opin Investig Drugs. 2004 Jan;5(1):76-81.Curr Opin Investig Drugs. 2004.PMID:14983978Review.
- [Nicotine acetylcholine receptors and neuropsychiatric disorders].Vázquez-Palacios G, Bonilla-Jaime H.Vázquez-Palacios G, et al.Rev Neurol. 2004 Dec 16-31;39(12):1146-60.Rev Neurol. 2004.PMID:15625635Review.Spanish.
- Central nicotinic receptors: structure, function, ligands, and therapeutic potential.Romanelli MN, Gratteri P, Guandalini L, Martini E, Bonaccini C, Gualtieri F.Romanelli MN, et al.ChemMedChem. 2007 Jun;2(6):746-67. doi: 10.1002/cmdc.200600207.ChemMedChem. 2007.PMID:17295372Review.
- Rationale, pharmacology and clinical efficacy of partial agonists of alpha4beta2 nACh receptors for smoking cessation.Rollema H, Coe JW, Chambers LK, Hurst RS, Stahl SM, Williams KE.Rollema H, et al.Trends Pharmacol Sci. 2007 Jul;28(7):316-25. doi: 10.1016/j.tips.2007.05.003. Epub 2007 Jun 18.Trends Pharmacol Sci. 2007.PMID:17573127Review.
Cited by
- α7-Nicotinic acetylcholine receptor: role in early odor learning preference in mice.Hellier JL, Arevalo NL, Smith L, Xiong KN, Restrepo D.Hellier JL, et al.PLoS One. 2012;7(4):e35251. doi: 10.1371/journal.pone.0035251. Epub 2012 Apr 13.PLoS One. 2012.PMID:22514723Free PMC article.
- Nicotine and nicotinic system in hypoglutamatergic models of schizophrenia.Tizabi Y.Tizabi Y.Neurotox Res. 2007 Dec;12(4):233-46. doi: 10.1007/BF03033907.Neurotox Res. 2007.PMID:18201951Review.
- Partial agonism of 5-HT3 receptors: a novel approach to the symptomatic treatment of IBS-D.Moore NA, Sargent BJ, Manning DD, Guzzo PR.Moore NA, et al.ACS Chem Neurosci. 2013 Jan 16;4(1):43-7. doi: 10.1021/cn300166c. Epub 2012 Dec 10.ACS Chem Neurosci. 2013.PMID:23342199Free PMC article.Review.
- Exploring determinants of agonist efficacy at the CB1 cannabinoid receptor: Analogues of the synthetic cannabinoid receptor agonist EG-018.Finlay DB, Nguyen T, Gamage TF, Chen S, Barrus DG, Patel PR, Thomas BF, Wiley JL, Zhang Y, Glass M.Finlay DB, et al.Pharmacol Res Perspect. 2022 Feb;10(1):e00901. doi: 10.1002/prp2.901.Pharmacol Res Perspect. 2022.PMID:35041297Free PMC article.
- Structural determinants for interaction of partial agonists with acetylcholine binding protein and neuronal alpha7 nicotinic acetylcholine receptor.Hibbs RE, Sulzenbacher G, Shi J, Talley TT, Conrod S, Kem WR, Taylor P, Marchot P, Bourne Y.Hibbs RE, et al.EMBO J. 2009 Oct 7;28(19):3040-51. doi: 10.1038/emboj.2009.227. Epub 2009 Aug 20.EMBO J. 2009.PMID:19696737Free PMC article.
Publication types
MeSH terms
Substances
Related information
LinkOut - more resources
Full Text Sources
Medical