2-Methyl-6-(phenylethynyl)pyridine

In today's world, 2-Methyl-6-(phenylethynyl)pyridine has acquired significant relevance in different areas, generating an impact that goes beyond what was expected. Since its emergence, 2-Methyl-6-(phenylethynyl)pyridine has captured the attention of experts and the general public, generating debates, research and diverse opinions that have marked its importance and scope in contemporary society. In this article, we will delve into the essence of 2-Methyl-6-(phenylethynyl)pyridine, exploring its implications, its evolution over time, and its influence in different spheres, demonstrating the impact that this unique figure/theme/date has on our current reality.
2-Methyl-6-(phenylethynyl)pyridine
Identifiers
  • 2-Methyl-6-(phenylethynyl)pyridine
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H11N
Molar mass193.249 g·mol−1
3D model (JSmol)
  • CC1=CC=CC(=N1)C#CC2=CC=CC=C2
  • InChI=1S/C14H11N.ClH/c1-12-6-5-9-14(15-12)11-10-13-7-3-2-4-8-13;/h2-9H,1H3;1H checkY
  • Key:PKDHDJBNEKXCBI-UHFFFAOYSA-N checkY
 ☒NcheckY (what is this?)  (verify)

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.[1] 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,[2][3] and as a positive allosteric modulator of another subtype mGlu4,[4] and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons.[5] It was also shown to produce antidepressant[6][7][8] and anxiolytic effects in animals,[9][10][11] and to reduce the effects of morphine withdrawal,[12] most likely due to direct interaction between mGluR5 and the μ-opioid receptor.[13]

The main significance of MPEP has been as a lead compound to develop more potent and selective mGluR5 antagonists such as MTEP,[14] but research using MPEP itself continues, and recently it was shown to reduce self-administration of nicotine,[15][16] cocaine,[17][18] ketamine and heroin in animals,[19] possibly through an MPEP-induced potentiation of the rewarding effect of the self-administered drug,[20] and MPEP was also shown to possess weak reinforcing effects by itself.[21]

See also

References

  1. ^ Micheli F (November 2000). "Methylphenylethynylpyridine (MPEP) Novartis". Current Opinion in Investigational Drugs. 1 (3): 355–9. PMID 11249719.
  2. ^ O'Leary DM, Movsesyan V, Vicini S, Faden AI (December 2000). "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. doi:10.1038/sj.bjp.0703715. PMC 1572472. PMID 11090117.
  3. ^ Movsesyan VA, O'Leary DM, Fan L, Bao W, Mullins PG, Knoblach SM, Faden AI (January 2001). "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. PMID 11123360.
  4. ^ Mathiesen JM, Svendsen N, Bräuner-Osborne H, Thomsen C, Ramirez MT (March 2003). "Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP". British Journal of Pharmacology. 138 (6): 1026–30. doi:10.1038/sj.bjp.0705159. PMC 1573757. PMID 12684257.
  5. ^ Pisani A, Gubellini P, Bonsi P, Conquet F, Picconi B, Centonze D, et al. (2001). "Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons". Neuroscience. 106 (3): 579–87. doi:10.1016/S0306-4522(01)00297-4. PMID 11591458. S2CID 38753726.
  6. ^ Li X, Need AB, Baez M, Witkin JM (October 2006). "Metabotropic glutamate 5 receptor antagonism is associated with antidepressant-like effects in mice". The Journal of Pharmacology and Experimental Therapeutics. 319 (1): 254–9. doi:10.1124/jpet.106.103143. PMID 16803860. S2CID 14632318.
  7. ^ Tatarczyńska E, Klodzińska A, Chojnacka-Wójcik E, Palucha A, Gasparini F, Kuhn R, Pilc A (April 2001). "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. doi:10.1038/sj.bjp.0703923. PMC 1572682. PMID 11264235.
  8. ^ Pilc A, Kłodzińska A, Brański P, Nowak G, Pałucha A, Szewczyk B, et al. (August 2002). "Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats". Neuropharmacology. 43 (2): 181–7. doi:10.1016/S0028-3908(02)00082-5. PMID 12213272. S2CID 23177632.
  9. ^ Kłodzińska A, Tatarczyńska E, Chojnacka-Wójcik E, Pilc A (2000). "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. PMID 11334240.
  10. ^ Ballard TM, Woolley ML, Prinssen E, Huwyler J, Porter R, Spooren W (April 2005). "The effect of the mGlu5 receptor antagonist MPEP in rodent tests of anxiety and cognition: a comparison". Psychopharmacology. 179 (1): 218–29. doi:10.1007/s00213-005-2211-9. PMID 15739074. S2CID 25136496.
  11. ^ Varty GB, Grilli M, Forlani A, Fredduzzi S, Grzelak ME, Guthrie DH, et al. (April 2005). "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. doi:10.1007/s00213-005-2143-4. PMID 15682298. S2CID 21807900.
  12. ^ Rasmussen K, Martin H, Berger JE, Seager MA (February 2005). "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. doi:10.1016/j.neuropharm.2004.09.010. PMID 15695156. S2CID 13552709.
  13. ^ Schröder H, Wu DF, Seifert A, Rankovic M, Schulz S, Höllt V, Koch T (March 2009). "Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the micro-opioid receptor". Neuropharmacology. 56 (4): 768–78. doi:10.1016/j.neuropharm.2008.12.010. PMID 19162047. S2CID 41530896.
  14. ^ Lea PM, Faden AI (2006). "Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP". CNS Drug Reviews. 12 (2): 149–66. doi:10.1111/j.1527-3458.2006.00149.x. PMC 6494124. PMID 16958988.
  15. ^ Paterson NE, Semenova S, Gasparini F, Markou A (May 2003). "The mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice". Psychopharmacology. 167 (3): 257–64. doi:10.1007/s00213-003-1432-z. PMID 12682710. S2CID 40627145.
  16. ^ Bespalov AY, Dravolina OA, Sukhanov I, Zakharova E, Blokhina E, Zvartau E, et al. (2005). "Metabotropic glutamate receptor (mGluR5) antagonist MPEP attenuated cue- and schedule-induced reinstatement of nicotine self-administration behavior in rats". Neuropharmacology. 49 (Suppl 1): 167–78. doi:10.1016/j.neuropharm.2005.06.007. PMID 16023685. S2CID 37283433.
  17. ^ Tessari M, Pilla M, Andreoli M, Hutcheson DM, Heidbreder CA (September 2004). "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. doi:10.1016/j.ejphar.2004.07.056. PMID 15363959.
  18. ^ Paterson NE, Markou A (April 2005). "The metabotropic glutamate receptor 5 antagonist MPEP decreased break points for nicotine, cocaine and food in rats". Psychopharmacology. 179 (1): 255–61. doi:10.1007/s00213-004-2070-9. PMID 15619120. S2CID 24096619.
  19. ^ van der Kam EL, de Vry J, Tzschentke TM (December 2007). "Effect of 2-methyl-6-(phenylethynyl) pyridine on intravenous self-administration of ketamine and heroin in the rat". Behavioural Pharmacology. 18 (8): 717–24. doi:10.1097/FBP.0b013e3282f18d58. PMID 17989509. S2CID 24990842.
  20. ^ van der Kam EL, De Vry J, Tzschentke TM (March 2009). "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. doi:10.1016/j.ejphar.2008.12.042. PMID 19210976.
  21. ^ van der Kam EL, De Vry J, Tzschentke TM (April 2009). "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. doi:10.1016/j.ejphar.2009.01.049. PMID 19326478.
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