3′-Fluoro substitution in the pyridine ring of epibatidine improves selectivity and efficacy for α4β2 versus α3β4 nAChRs

Neuropharmacology

Volumn 55, Issue 8, 2008, Pages 1287-1292

  Abdrakhmanova, Galya R ^a,b   Ivy Carroll, F ^a,b   Damaj, M I ^a,b   Martin, Billy R ^a,b  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b RTI INTERNATIONAL   (United States)

Author keywords

Binding; Epibatidine; Epibatidine analogs; Nicotine induced analgesia; Recombinant neuronal nicotinic receptors; Whole cell

Indexed keywords

3' FLUOROEPIBATIDINE; BUNGAROTOXIN RECEPTOR; EPIBATIDINE; NICOTINIC RECEPTOR; NICOTINIC RECEPTOR ALPHA3BETA4; NICOTINIC RECEPTOR ALPHA4BETA2; RTI 31; UNCLASSIFIED DRUG; ACETYLCHOLINE; DIHYDRO BETA ERYTHROIDINE; FUSED HETEROCYCLIC RINGS; NICOTINIC AGENT; PYRIDINE; PYRIDINE DERIVATIVE;

ANALGESIC ACTIVITY; ANTINOCICEPTION; ARTICLE; BINDING ASSAY; CONCENTRATION RESPONSE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DRUG CONFORMATION; DRUG EFFICACY; DRUG MECHANISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SELECTIVITY; HUMAN; HUMAN CELL; IC 50; PATCH CLAMP; PRIORITY JOURNAL; RECEPTOR AFFINITY; BINDING COMPETITION; CELL LINE; CELL MEMBRANE POTENTIAL; CHEMISTRY; DOSE RESPONSE; DRUG EFFECT; GENETIC TRANSFECTION; GENETICS; METABOLISM; METHODOLOGY; STRUCTURE ACTIVITY RELATION;

ACETYLCHOLINE; BICYCLO COMPOUNDS, HETEROCYCLIC; BINDING, COMPETITIVE; CELL LINE, TRANSFORMED; DIHYDRO-BETA-ERYTHROIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MEMBRANE POTENTIALS; NICOTINIC AGONISTS; PATCH-CLAMP TECHNIQUES; PYRIDINES; RECEPTORS, NICOTINIC; STRUCTURE-ACTIVITY RELATIONSHIP; TRANSFECTION;

EID: 56249124209     PISSN: 00283908     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.neuropharm.2008.08.007     Document Type: Article

References (49)

1. Abdrakhmanova, G., Carroll, F.I., Damaj, M.I., Martin, B.R., 2007. Functional examination of epibatidine analogs with substitutions at the 3′ position of the pyridine ring in alpha4beta2, alpha7 and alpha3beta4 nAChR subtypes. Annual Neuroscience Meeting 2007.
2. Abdrakhmanova G., Damaj M.I., Carroll F.I., and Martin B.R. 2-Fluoro-3-(4-nitro-phenyl)deschloroepibatidine is a novel potent competitive antagonist of human neuronal {alpha}4{beta}2 nAChRs. Mol. Pharmacol. 69 (2006) 1945-1952
3. Abdrakhmanova G., Dorfman J., Xiao Y., and Morad M. Protons enhance the gating kinetics of the alpha3/beta4 neuronal nicotinic acetylcholine receptor by increasing its apparent affinity to agonists. Mol. Pharmacol. 61 (2002) 369-378
4. Albuquerque E.X., Pereira E.F., Mike A., Eisenberg H.M., Maelicke A., and Alkondon M. Neuronal nicotinic receptors in synaptic functions in humans and rats: physiological and clinical relevance [in process citation]. Behav. Brain Res. 113 (2000) 131-141
5. Avalos M., Parker M.J., Maddox F.N., Carroll F.I., and Luetje C.W. Effects of pyridine ring substitutions on affinity, efficacy, and subtype selectivity of neuronal nicotinic receptor agonist epibatidine. J. Pharmacol. Exp. Ther. 302 (2002) 1246-1252
6. Badio B., and Daly J.W. Epibatidine, a potent analgetic and nicotinic agonist. Mol. Pharmacol. 45 (1994) 563-569
7. Buisson B., Vallejo Y.F., Green W.N., and Bertrand D. The unusual nature of epibatidine responses at the alpha4beta2 nicotinic acetylcholine receptor. Neuropharmacology 39 (2000) 2561-2569
8. Carroll F.I. Epibatidine structure-activity relationships. Bioorg. Med. Chem. Lett. 14 (2004) 1889-1896
9. Carroll F.I., Lee J.R., Navarro H.A., Brieaddy L.E., Abraham P., Damaj M.I., and Martin B.R. Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2′-substituted-3′-phenyl-5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes. Novel nicotinic antagonist. J. Med. Chem. 44 (2001) 4039-4041
10. Carroll F.I., Lee J.R., Navarro H.A., Ma W., Brieaddy L.E., Abraham P., Damaj M.I., and Martin B.R. Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2′,3'-disubstituted 5′-pyridinyl)-7-azabicyclo[2.2.1]heptanes: epibatidine analogues. J. Med. Chem. 45 (2002) 4755-4761
11. Criado M., Mulet J., Bernal J.A., Gerber S., Sala S., and Sala F. Mutations of a conserved lysine residue in the N-terminal domain of alpha7 nicotinic receptors affect gating and binding of nicotinic agonists. Mol. Pharmacol. 68 (2005) 1669-1677
12. Daly J.W., Garraffo H.M., Spande T.F., Decker M.W., Sullivan J.P., and Williams M. Alkaloids from frog skin: the discovery of epibatidine and the potential for developing novel non-opioid analgesics. Nat. Prod. Rep. 17 (2000) 131-135
13. Damaj M.I., Meyer E.M., and Martin B.R. The antinociceptive effects of alpha7 nicotinic agonists in an acute pain model. Neuropharmacology 39 (2000) 2785-2791
14. Dani J.A., and Bertrand D. Nicotinic acetylcholine receptors and nicotinic cholinergic mechanisms of the central nervous system. Ann. Rev. Pharmacol. Toxicol. 47 (2007) 699-729
15. De Biasi M. Nicotinic mechanisms in the autonomic control of organ systems. J. Neurobiol. 53 (2002) 568-579
16. Dickinson J.A., Kew J.N., and Wonnacott S. Presynaptic {alpha}7 and {beta}2-containing nicotinic acetylcholine receptors modulate excitatory amino acid release from rat prefrontal cortex nerve terminals via distinct cellular mechanisms. Mol. Pharmacol. (2008)
17. Drapeau P., and Legendre P. Neuromuscular transmission on the rebound. Receptors Channels 7 (2001) 491-496
18. Eaton J.B., Peng J.H., Schroeder K.M., George A.A., Fryer J.D., Krishnan C., Buhlman L., Kuo Y.P., Steinlein O., and Lukas R.J. Characterization of human alpha 4 beta 2-nicotinic acetylcholine receptors stably and heterologously expressed in native nicotinic receptor-null SH-EP1 human epithelial cells. Mol. Pharmacol. 64 (2003) 1283-1294
19. Flores C.M., DeCamp R.M., Kilo S., Rogers S.W., and Hargreaves K.M. Neuronal nicotinic receptor expression in sensory neurons of the rat trigeminal ganglion: demonstration of alpha3beta4, a novel subtype in the mammalian nervous system. J. Neurosci. 16 (1996) 7892-7901
20. Flores C.M., Rogers S.W., Pabreza L.A., Wolfe B.B., and Kellar K.J. A subtype of nicotinic cholinergic receptor in rat brain is composed of alpha 4 and beta 2 subunits and is up-regulated by chronic nicotine treatment. Mol. Pharmacol. 41 (1992) 31-37
21. Genzen J.R., Van Cleve W., and McGehee D.S. Dorsal root ganglion neurons express multiple nicotinic acetylcholine receptor subtypes. J. Neurophysiol. 86 (2001) 1773-1782
22. Gotti C., Riganti L., Vailati S., and Clementi F. Brain neuronal nicotinic receptors as new targets for drug discovery. Curr. Pharm. Des. 12 (2006) 407-428
23. Gotti C., Zoli M., and Clementi F. Brain nicotinic acetylcholine receptors: native subtypes and their relevance. Trends Pharmacol. Sci. 27 (2006) 482-491
24. Huang Y., Zhu Z., Xiao Y., and Laruelle M. Epibatidine analogues as selective ligands for the alpha(x)beta2-containing subtypes of nicotinic acetylcholine receptors. Bioorg. Med. Chem. Lett. 15 (2005) 4385-4388
25. Keath J.R., Iacoviello M.P., Barrett L.E., Mansvelder H.D., and McGehee D.S. Differential modulation by nicotine of substantia nigra versus ventral tegmental area dopamine neurons. J. Neurophysiol. 98 (2007) 3388-3396
26. Levin E.D., Bradley A., Addy N., and Sigurani N. Hippocampal alpha 7 and alpha 4 beta 2 nicotinic receptors and working memory. Neuroscience 109 (2002) 757-765
27. Lindovsky J., Kaniakova M., Svobodova L., Vyskocil F., and Krusek J. Role of negatively charged amino acids in beta 4 F-loop in activation and desensitization of alpha 3 beta 4 rat neuronal nicotinic receptors. Biochim. Biophys. Acta 1778 (2008) 864-871
28. Lips K.S., Konig P., Schatzle K., Pfeil U., Krasteva G., Spies M., Haberberger R.V., Grando S.A., and Kummer W. Coexpression and spatial association of nicotinic acetylcholine receptor subunits alpha7 and alpha10 in rat sympathetic neurons. J. Mol. Neurosci. 30 (2006) 15-16
29. Liu Q., Kawai H., and Berg D.K. beta-Amyloid peptide blocks the response of alpha 7-containing nicotinic receptors on hippocampal neurons. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 4734-4739
30. Liu Q., Yu K.W., Chang Y.C., Lukas R.J., and Wu J. Agonist-induced hump current production in heterologously-expressed human alpha4beta2-nicotinic acetylcholine receptors. Acta Pharmacol. Sin. 29 (2008) 305-319
31. Marubio L.M., del Mar Arroyo-Jimenez M., Cordero-Erausquin M., Lena C., Le Novere N., de Kerchove d'Exaerde A., Huchet M., Damaj M.I., and Changeux J.P. Reduced antinociception in mice lacking neuronal nicotinic receptor subunits. Nature 398 (1999) 805-810
32. Meyer E.L., Xiao Y., and Kellar K.J. Agonist regulation of rat alpha 3 beta 4 nicotinic acetylcholine receptors stably expressed in human embryonic kidney 293 cells. Mol. Pharmacol. 60 (2001) 568-576
33. Moaddel R., Oliveira R.V., Kimura T., Hyppolite P., Juhaszova M., Xiao Y., Kellar K.J., Bernier M., and Wainer I.W. Initial synthesis and characterization of an alpha7 nicotinic receptor cellular membrane affinity chromatography column: effect of receptor subtype and cell type. Anal. Chem. 80 (2008) 48-54
34. Moroni M., Zwart R., Sher E., Cassels B.K., and Bermudez I. alpha4beta2 nicotinic receptors with high and low acetylcholine sensitivity: pharmacology, stoichiometry, and sensitivity to long-term exposure to nicotine. Mol. Pharmacol. 70 (2006) 755-768
35. Perry D.C., Xiao Y., Nguyen H.N., Musachio J.L., Davila-Garcia M.I., and Kellar K.J. Measuring nicotinic receptors with characteristics of alpha4beta2, alpha3beta2 and alpha3beta4 subtypes in rat tissues by autoradiography. J. Neurochem. 82 (2002) 468-481
36. Picciotto M.R., and Zoli M. Neuroprotection via nAChRs: the role of nAChRs in neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Front Biosci. 13 (2008) 492-504
37. Picciotto M.R., Zoli M., Lena C., Bessis A., Lallemand Y., Le Novere N., Vincent P., Pich E.M., Brulet P., and Changeux J.P. Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain. Nature 374 (1995) 65-67
38. Quick M.W., Ceballos R.M., Kasten M., McIntosh J.M., and Lester R.A. Alpha3beta4 subunit-containing nicotinic receptors dominate function in rat medial habenula neurons. Neuropharmacology 38 (1999) 769-783
39. Romanelli M.N., Gratteri P., Guandalini L., Martini E., Bonaccini C., and Gualtieri F. Central nicotinic receptors: structure, function, ligands, and therapeutic potential. ChemMedChem (2007)
40. Spang J.E., Bertrand S., Westera G., Patt J.T., Schubiger P.A., and Bertrand D. Chemical modification of epibatidine causes a switch from agonist to antagonist and modifies its selectivity for neuronal nicotinic acetylcholine receptors. Chem. Biol. 7 (2000) 545-555
41. Sullivan J.P., and Bannon A.W. Epibatidine: pharmacological properties of a novel nicotinic acetylcholine receptor agonist and analgesic agent. CNS Drug Rev. 2 (1996) 21-39
42. Sullivan J.P., Decker M.W., Donnelly-Roberts D., Brioni J.D., Bannon A.W., Holladay M.W., Anderson D.J., Briggs C.A., Williams M., and Arneric S.P. Cholinergic channel activators: novel opportunities for the treatment of CNS disorders. Proc. West Pharmacol. Soc. 38 (1995) 127-130
43. Wang N., Orr-Urtreger A., Chapman J., Rabinowitz R., and Korczyn A.D. Deficiency of nicotinic acetylcholine receptor beta 4 subunit causes autonomic cardiac and intestinal dysfunction. Mol. Pharmacol. 63 (2003) 574-580
44. Wei Z.L., Xiao Y., Yuan H., Baydyuk M., Petukhov P.A., Musachio J.L., Kellar K.J., and Kozikowski A.P. Novel pyridyl ring C5 substituted analogues of epibatidine and 3-(1-methyl-2(S)-pyrrolidinylmethoxy)pyridine (A-84543) as highly selective agents for neuronal nicotinic acetylcholine receptors containing beta2 subunits. J. Med. Chem. 48 (2005) 1721-1724
45. Whiting P., and Lindstrom J. Purification and characterization of a nicotinic acetylcholine receptor from rat brain. Proc. Natl. Acad. Sci. U.S.A. 84 (1987) 595-599
46. Wooltorton J.R., Pidoplichko V.I., Broide R.S., and Dani J.A. Differential desensitization and distribution of nicotinic acetylcholine receptor subtypes in midbrain dopamine areas. J. Neurosci. 23 (2003) 3176-3185
47. Wu J., Kuo Y.P., George A.A., Xu L., Hu J., and Lukas R.J. beta-Amyloid directly inhibits human alpha4beta2-nicotinic acetylcholine receptors heterologously expressed in human SH-EP1 cells. J. Biol. Chem. 279 (2004) 37842-37851
48. Xiao Y., Meyer E.L., Thompson J.M., Surin A., Wroblewski J., and Kellar K.J. Rat alpha3/beta4 subtype of neuronal nicotinic acetylcholine receptor stably expressed in a transfected cell line: pharmacology of ligand binding and function. Mol. Pharmacol. 54 (1998) 322-333
49. 2+ permeation of stably transfected alpha3/beta4 neuronal nicotinic acetylcholine receptor. Mol. Pharmacol. 55 (1999) 970-981