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Alpha-7 nicotinic receptor: Wikis

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Molecular model of the alpha7 nicotinic receptor.

The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor, consisting entirely of α7 subunits.[1]. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].

It is located in the brain, where activation yields post- and presynaptic excitation[1], mainly by increased Ca2+ permeability.

Contents

Ligands

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Agonists

PAMs

At least two types of positive allosteric modulators (PAMs) can be distinguished.[9]

  • PNU-120,596 [10]
  • NS-1738: marginal effects on α7 desensitization kinetics; modestly brain-penetrant[11]
  • XY4083: unlike the above PAMs, XY4083 does not affect α7 desensitization kinetics, and is readily brain penetrant. Improves cognitive behavior in animal models[12]
  • A-867744 [13][14]

Antagonists

  • α-conotoxin ArIB[V11L,V16D]: potent and highly subtype-selective; slowly reversible[15]
  • Quinolizidine (–)-1-epi-207I: α7 subtype preferring blocker[16]

See also

References

  1. ^ a b Pharmacology, (Rang, Dale, Ritter & Moore, ISBN 0443071454, 5:th ed., Churchill Livingstone 2003) Page 138.
  2. ^ Mazurov A, Klucik J, Miao L, et al. (2005). "2-(Arylmethyl)-3-substituted quinuclidines as selective alpha 7 nicotinic receptor ligands". Bioorg. Med. Chem. Lett. 15 (8): 2073–7. doi:10.1016/j.bmcl.2005.02.045. PMID 15808471. 
  3. ^ Tietje KR, Anderson DJ, Bitner RS, et al. (2008). "Preclinical characterization of A-582941: a novel alpha7 neuronal nicotinic receptor agonist with broad spectrum cognition-enhancing properties". CNS Neurosci Ther 14 (1): 65–82. doi:10.1111/j.1527-3458.2008.00037.x. PMID 18482100. 
  4. ^ Marrero MB, Papke RL, Bhatti BS, Shaw S, Bencherif M (2004). "The neuroprotective effect of 2-(3-pyridyl)-1-azabicyclo[3.2.2]nonane (TC-1698), a novel alpha7 ligand, is prevented through angiotensin II activation of a tyrosine phosphatase". J. Pharmacol. Exp. Ther. 309 (1): 16–27. doi:10.1124/jpet.103.061655. PMID 14722323. 
  5. ^ Acker BA, Jacobsen EJ, Rogers BN, et al. (2008). "Discovery of N-[(3R,5R)-1-azabicyclo[3.2.1]oct-3-yl] furo[2,3-c]pyridine-5-carboxamide as an agonist of the alpha7 nicotinic acetylcholine receptor: in vitro and in vivo activity". Bioorg. Med. Chem. Lett. 18 (12): 3611–5. doi:10.1016/j.bmcl.2008.04.070. PMID 18490160. 
  6. ^ Walker DP, Wishka DG, Piotrowski DW, et al. (2006). "Design, synthesis, structure-activity relationship, and in vivo activity of azabicyclic aryl amides as alpha7 nicotinic acetylcholine receptor agonists". Bioorg. Med. Chem. 14 (24): 8219–48. doi:10.1016/j.bmc.2006.09.019. PMID 17011782. 
  7. ^ Biton B, Bergis OE, Galli F, et al. (2007). "SSR180711, a novel selective alpha7 nicotinic receptor partial agonist: (1) binding and functional profile". Neuropsychopharmacology 32 (1): 1–16. doi:10.1038/sj.npp.1301189. PMID 17019409. 
  8. ^ Macor JE, Gurley D, Lanthorn T, et al. (2001). "The 5-HT3 antagonist tropisetron (ICS 205-930) is a potent and selective alpha7 nicotinic receptor partial agonist". Bioorg. Med. Chem. Lett. 11 (3): 319–21. doi:10.1016/S0960-894X(00)00670-3. PMID 11212100. http://linkinghub.elsevier.com/retrieve/pii/S0960894X00006703. 
  9. ^ Grønlien JH, Håkerud M, Ween H, et al. (2007). "Distinct profiles of alpha7 nAChR positive allosteric modulation revealed by structurally diverse chemotypes". Mol. Pharmacol. 72 (3): 715–24. doi:10.1124/mol.107.035410. PMID 17565004. 
  10. ^ Hurst RS, Hajós M, Raggenbass M, et al. (2005). "A novel positive allosteric modulator of the alpha7 neuronal nicotinic acetylcholine receptor: in vitro and in vivo characterization". J. Neurosci. 25 (17): 4396–405. doi:10.1523/JNEUROSCI.5269-04.2005. PMID 15858066. 
  11. ^ Timmermann DB, Grønlien JH, Kohlhaas KL, et al. (2007). "An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo". J. Pharmacol. Exp. Ther. 323 (1): 294–307. doi:10.1124/jpet.107.120436. PMID 17625074. 
  12. ^ Ng, HJ, et al. (2007). "Nootropic α7 nicotinic receptor allosteric modulator derived from GABA A receptor modulators". PNAS 104 (19): 8059–8064. doi:10.1073/pnas.0701321104. 
  13. ^ Faghih R, Gopalakrishnan SM, Gronlien JH, et al. (May 2009). "Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl)benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor". J. Med. Chem. 52 (10): 3377–84. doi:10.1021/jm9003818. PMID 19419141. 
  14. ^ Malysz J, Gronlien JH, Anderson DJ, et al. (April 2009). "In vitro pharmacological characterization of a novel allosteric modulator of {alpha}7 nAChR, A-867744, exhibiting unique pharmacological profile". J. Pharmacol. Exp. Ther.. doi:10.1124/jpet.109.151886. PMID 19389923. 
  15. ^ Whiteaker P, Christensen S, Yoshikami D, et al. (2007). "Discovery, synthesis, and structure activity of a highly selective alpha7 nicotinic acetylcholine receptor antagonist". Biochemistry 46 (22): 6628–38. doi:10.1021/bi7004202. PMID 17497892. 
  16. ^ Tsuneki H, You Y, Toyooka N, et al. (2004). "Alkaloids indolizidine 235B', quinolizidine 1-epi-207I, and the tricyclic 205B are potent and selective noncompetitive inhibitors of nicotinic acetylcholine receptors". Mol. Pharmacol. 66 (4): 1061–9. doi:10.1124/mol.104.000729. PMID 15258256. 

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