2-Methyl-6-(phenylethynyl)pyridine

Chemical compound changed 477214380 2-Methyl-6-(phenylethynyl)pyridine Methylphenylethynylpyridine.svg skin-invert-image 200 changed ?? 96206-92-7 3025961 changed FDA 7VC0YVI27Y 1426 correct drugbank correct chemspider 7970355 14 11 1 CC1=CC=CC(=N1)C#CC2=CC=CC=C2 correct chemspider 1S/C14H11N.ClH/c1-12-6-5-9-14(15-12)11-10-13-7-3-2-4-8-13;/h2-9H,1H3;1H correct chemspider PKDHDJBNEKXCBI-UHFFFAOYSA-N 2-Methyl-6-(phenylethynyl)pyridine (MPEP) is a research drug which was one of the first compounds found to act as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. After being originally patented as a liquid crystal for LCDs, it was developed by the pharmaceutical company Novartis in the late 1990s. Micheli F Methylphenylethynylpyridine (MPEP) Novartis Current Opinion in Investigational Drugs 1 3 355–9 November 2000 11249719 It was found to produce neuroprotective effects following acute brain injury in animal studies, although it was unclear whether these results were purely from mGluR5 blockade as it also acts as a weak NMDA antagonist, O'Leary DM, Movsesyan V, Vicini S, Faden AI Selective mGluR5 antagonists MPEP and SIB-1893 decrease NMDA or glutamate-mediated neuronal toxicity through actions that reflect NMDA receptor antagonism British Journal of Pharmacology 131 7 1429–37 December 2000 11090117 1572472 10.1038/sj.bjp.0703715 Movsesyan VA, O'Leary DM, Fan L, Bao W, Mullins PG, Knoblach SM, Faden AI mGluR5 antagonists 2-methyl-6-(phenylethynyl)-pyridine and (E)-2-methyl-6-(2-phenylethenyl)-pyridine reduce traumatic neuronal injury in vitro and in vivo by antagonizing N-methyl-D-aspartate receptors The Journal of Pharmacology and Experimental Therapeutics 296 1 41–7 January 2001 11123360 and as a positive allosteric modulator of another subtype mGluR4, Mathiesen JM, Svendsen N, Bräuner-Osborne H, Thomsen C, Ramirez MT Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP British Journal of Pharmacology 138 6 1026–30 March 2003 12684257 1573757 10.1038/sj.bjp.0705159 and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons. Pisani A, Gubellini P, Bonsi P, Conquet F, Picconi B, Centonze D, Bernardi G, Calabresi P 6 Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons Neuroscience 106 3 579–87 2001 11591458 10.1016/S0306-4522(01)00297-4 38753726 It was also shown to produce antidepressant Li X, Need AB, Baez M, Witkin JM Metabotropic glutamate 5 receptor antagonism is associated with antidepressant-like effects in mice The Journal of Pharmacology and Experimental Therapeutics 319 1 254–9 October 2006 16803860 10.1124/jpet.106.103143 14632318 Tatarczyńska E, Klodzińska A, Chojnacka-Wójcik E, Palucha A, Gasparini F, Kuhn R, Pilc A Potential anxiolytic- and antidepressant-like effects of MPEP, a potent, selective and systemically active mGlu5 receptor antagonist British Journal of Pharmacology 132 7 1423–30 April 2001 11264235 1572682 10.1038/sj.bjp.0703923 Pilc A, Kłodzińska A, Brański P, Nowak G, Pałucha A, Szewczyk B, Tatarczyńska E, Chojnacka-Wójcik E, Wierońska JM 6 Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats Neuropharmacology 43 2 181–7 August 2002 12213272 10.1016/S0028-3908(02)00082-5 23177632 and anxiolytic effects in animals, Kłodzińska A, Tatarczyńska E, Chojnacka-Wójcik E, Pilc A Anxiolytic-like effects of group I metabotropic glutamate antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) in rats Polish Journal of Pharmacology 52 6 463–6 2000 11334240 Ballard TM, Woolley ML, Prinssen E, Huwyler J, Porter R, Spooren W The effect of the mGlu5 receptor antagonist MPEP in rodent tests of anxiety and cognition: a comparison Psychopharmacology 179 1 218–29 April 2005 15739074 10.1007/s00213-005-2211-9 25136496 Varty GB, Grilli M, Forlani A, Fredduzzi S, Grzelak ME, Guthrie DH, Hodgson RA, Lu SX, Nicolussi E, Pond AJ, Parker EM, Hunter JC, Higgins GA, Reggiani A, Bertorelli R 6 The antinociceptive and anxiolytic-like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: a comparison of efficacy and side-effect profiles Psychopharmacology 179 1 207–17 April 2005 15682298 10.1007/s00213-005-2143-4 21807900 and to reduce the effects of morphine withdrawal, Rasmussen K, Martin H, Berger JE, Seager MA The mGlu5 receptor antagonists MPEP and MTEP attenuate behavioral signs of morphine withdrawal and morphine-withdrawal-induced activation of locus coeruleus neurons in rats Neuropharmacology 48 2 173–80 February 2005 15695156 10.1016/j.neuropharm.2004.09.010 13552709 most likely due to direct interaction between mGluR5 and the μ-opioid receptor. Schröder H, Wu DF, Seifert A, Rankovic M, Schulz S, Höllt V, Koch T Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the micro-opioid receptor Neuropharmacology 56 4 768–78 March 2009 19162047 10.1016/j.neuropharm.2008.12.010 41530896 The main significance of MPEP has been as a lead compound to develop more potent and selective mGluR5 antagonists such as MTEP, Lea PM, Faden AI Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP CNS Drug Reviews 12 2 149–66 2006 16958988 6494124 10.1111/j.1527-3458.2006.00149.x but research using MPEP itself continues, and recently it was shown to reduce self-administration of nicotine, Paterson NE, Semenova S, Gasparini F, Markou A The mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice Psychopharmacology 167 3 257–64 May 2003 12682710 10.1007/s00213-003-1432-z 40627145 Bespalov AY, Dravolina OA, Sukhanov I, Zakharova E, Blokhina E, Zvartau E, Danysz W, van Heeke G, Markou A 6 Metabotropic glutamate receptor (mGluR5) antagonist MPEP attenuated cue- and schedule-induced reinstatement of nicotine self-administration behavior in rats Neuropharmacology 49 167–78 2005 Suppl 1 16023685 10.1016/j.neuropharm.2005.06.007 37283433 cocaine, Tessari M, Pilla M, Andreoli M, Hutcheson DM, Heidbreder CA Antagonism at metabotropic glutamate 5 receptors inhibits nicotine- and cocaine-taking behaviours and prevents nicotine-triggered relapse to nicotine-seeking European Journal of Pharmacology 499 1–2 121–33 September 2004 15363959 10.1016/j.ejphar.2004.07.056 Paterson NE, Markou A The metabotropic glutamate receptor 5 antagonist MPEP decreased break points for nicotine, cocaine and food in rats Psychopharmacology 179 1 255–61 April 2005 15619120 10.1007/s00213-004-2070-9 24096619 ketamine and heroin in animals, van der Kam EL, de Vry J, Tzschentke TM Effect of 2-methyl-6-(phenylethynyl) pyridine on intravenous self-administration of ketamine and heroin in the rat Behavioural Pharmacology 18 8 717–24 December 2007 17989509 10.1097/FBP.0b013e3282f18d58 24990842 possibly through an MPEP-induced potentiation of the rewarding effect of the self-administered drug, van der Kam EL, De Vry J, Tzschentke TM 2-Methyl-6-(phenylethynyl)-pyridine (MPEP) potentiates ketamine and heroin reward as assessed by acquisition, extinction, and reinstatement of conditioned place preference in the rat European Journal of Pharmacology 606 1–3 94–101 March 2009 19210976 10.1016/j.ejphar.2008.12.042 and MPEP was also shown to possess weak reinforcing effects by itself. van der Kam EL, De Vry J, Tzschentke TM The mGlu5 receptor antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) supports intravenous self-administration and induces conditioned place preference in the rat European Journal of Pharmacology 607 1–3 114–20 April 2009 19326478 10.1016/j.ejphar.2009.01.049 See also MTEP Fenobam MFZ 10-7 References 2 Category:Alkyne derivatives Category:Disubstituted pyridines Category:MGlu4 receptor agonists Category:MGlu5 receptor antagonists Category:Phenyl compounds