BQCA — Mediated Wiki

{{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox drug | IUPAC_name = 1-[(4-methoxyphenyl)methyl]-4-oxoquinoline-3-carboxylic acid | image = BQCA.svg | image_class = skin-invert-image | width =

| tradename = | routes_of_administration =

| C=18 | H=15 | N=1 | O=4 | smiles = COC1=CC=C(C=C1)CN2C=C(C(=O)C3=CC=CC=C32)C(=O)O | StdInChI = 1S/C18H15NO4/c1-23-13-8-6-12(7-9-13)10-19-11-15(18(21)22)17(20)14-4-2-3-5-16(14)19/h2-9,11H,10H2,1H3,(H,21,22) | StdInChIKey = BZBBTGCKPRSPGF-UHFFFAOYSA-N }}

'''BQCA''' ('''benzyl quinolone carboxylic acid''') is an experimental drug that acts as a potent and selective positive allosteric modulator of the Muscarinic acetylcholine receptor M1. It was one of the first M1-selective positive allosteric modulators to be discovered, originally developed as a potential treatment agent for cognitive symptoms of schizophrenia, and while BQCA itself was not adopted for clinical use due to its poor side effect profile it is still used in research, and has led to the discovery of a wide range of structurally related M1 PAMs.<ref>{{cite journal | vauthors = Ma L, Seager MA, Wittmann M, Jacobson M, Bickel D, Burno M, Jones K, Graufelds VK, Xu G, Pearson M, McCampbell A, Gaspar R, Shughrue P, Danziger A, Regan C, Flick R, Pascarella D, Garson S, Doran S, Kreatsoulas C, Veng L, Lindsley CW, Shipe W, Kuduk S, Sur C, Kinney G, Seabrook GR, Ray WJ | title = Selective activation of the M1 muscarinic acetylcholine receptor achieved by allosteric potentiation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 37 | pages = 15950–15955 | date = September 2009 | pmid = 19717450 | pmc = 2732705 | doi = 10.1073/pnas.0900903106 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Shirey JK, Brady AE, Jones PJ, Davis AA, Bridges TM, Kennedy JP, Jadhav SB, Menon UN, Xiang Z, Watson ML, Christian EP, Doherty JJ, Quirk MC, Snyder DH, Lah JJ, Levey AI, Nicolle MM, Lindsley CW, Conn PJ | title = A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning | journal = The Journal of Neuroscience| volume = 29 | issue = 45 | pages = 14271–14286 | date = November 2009 | pmid = 19906975 | pmc = 2811323 | doi = 10.1523/JNEUROSCI.3930-09.2009 }}</ref><ref>{{cite journal | vauthors = Thomsen M, Lindsley CW, Conn PJ, Wessell JE, Fulton BS, Wess J, Caine SB | title = Contribution of both M1 and M4 receptors to muscarinic agonist-mediated attenuation of the cocaine discriminative stimulus in mice | journal = Psychopharmacology | volume = 220 | issue = 4 | pages = 673–685 | date = April 2012 | pmid = 21964721 | pmc = 3314162 | doi = 10.1007/s00213-011-2516-9 }}</ref><ref>{{cite journal | vauthors = Chambon C, Jatzke C, Wegener N, Gravius A, Danysz W | title = Using cholinergic M1 receptor positive allosteric modulators to improve memory via enhancement of brain cholinergic communication | journal = European Journal of Pharmacology | volume = 697 | issue = 1–3 | pages = 73–80 | date = December 2012 | pmid = 23085025 | doi = 10.1016/j.ejphar.2012.10.011 }}</ref><ref>{{cite journal | vauthors = Mistry SN, Valant C, Sexton PM, Capuano B, Christopoulos A, Scammells PJ | title = Synthesis and pharmacological profiling of analogues of benzyl quinolone carboxylic acid (BQCA) as allosteric modulators of the M1 muscarinic receptor | journal = Journal of Medicinal Chemistry | volume = 56 | issue = 12 | pages = 5151–5172 | date = June 2013 | pmid = 23718562 | doi = 10.1021/jm400540b | url = http://eprints.nottingham.ac.uk/30413/ }}</ref><ref>{{cite journal | vauthors = Kuduk SD, Beshore DC | title = SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs) | journal = Current Topics in Medicinal Chemistry | date = 2014 | volume = 14 | issue = 15 | pages = 1738–1754 | pmid = 25176125 | doi = 10.2174/1568026614666140826120224 }}</ref><ref>{{cite journal | vauthors = Abdul-Ridha A, López L, Keov P, Thal DM, Mistry SN, Sexton PM, Lane JR, Canals M, Christopoulos A | title = Molecular determinants of allosteric modulation at the M1 muscarinic acetylcholine receptor | journal = The Journal of Biological Chemistry | volume = 289 | issue = 9 | pages = 6067–6079 | date = February 2014 | pmid = 24443568 | pmc = 3937673 | doi = 10.1074/jbc.M113.539080 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Choy KH, Shackleford DM, Malone DT, Mistry SN, Patil RT, Scammells PJ, Langmead CJ, Pantelis C, Sexton PM, Lane JR, Christopoulos A | title = Positive Allosteric Modulation of the Muscarinic M1 Receptor Improves Efficacy of Antipsychotics in Mouse Glutamatergic Deficit Models of Behavior | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 359 | issue = 2 | pages = 354–365 | date = November 2016 | pmid = 27630144 | doi = 10.1124/jpet.116.235788 | url = https://research.monash.edu/en/publications/f51cdde4-7937-4385-b8ae-1412808fd9d6 }}</ref><ref>{{cite journal | vauthors = Khajehali E, Valant C, Jörg M, Tobin AB, Conn PJ, Lindsley CW, Sexton PM, Scammells PJ, Christopoulos A | title = Probing the binding site of novel selective positive allosteric modulators at the M<sub>1</sub> muscarinic acetylcholine receptor | journal = Biochemical Pharmacology | volume = 154 | pages = 243–254 | date = August 2018 | pmid = 29777683 | pmc = 6066355 | doi = 10.1016/j.bcp.2018.05.009 }}</ref><ref>{{cite journal | vauthors = Lehner KR, Silverman HA, Addorisio ME, Roy A, Al-Onaizi MA, Levine Y, Olofsson PS, Chavan SS, Gros R, Nathanson NM, Al-Abed Y, Metz CN, Prado VF, Prado MA, Tracey KJ, Pavlov VA | title = Forebrain Cholinergic Signaling Regulates Innate Immune Responses and Inflammation | journal = Frontiers in Immunology | date = 2019 | volume = 10 | page = 585 | pmid = 31024522 | pmc = 6455130 | doi = 10.3389/fimmu.2019.00585 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Ishioh M, Nozu T, Miyagishi S, Igarashi S, Funayama T, Ohhira M, Okumura T | title = Activation of basal forebrain cholinergic neurons improves colonic hyperpermeability through the vagus nerve and adenosine A2B receptors in rats | journal = Biochemical Pharmacology | volume = 206 | article-number = 115331 | date = December 2022 | pmid = 36330948 | doi = 10.1016/j.bcp.2022.115331 }}</ref>

== References == {{Reflist}}

Category:Experimental drugs Category:Carboxylic acids Category:Quinolines Category:4-Methoxyphenyl compounds