Chemistry:2-Methyl-6-(phenylethynyl)pyridine

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Short description: Chemical compound
2-Methyl-6-(phenylethynyl)pyridine
Methylphenylethynylpyridine.svg
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
Chemical and physical data
FormulaC14H11N
Molar mass193.249 g·mol−1
3D model (JSmol)
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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. ↑ "Methylphenylethynylpyridine (MPEP) Novartis". Current Opinion in Investigational Drugs 1 (3): 355–9. November 2000. PMID 11249719. 
  2. ↑ "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. doi:10.1038/sj.bjp.0703715. PMID 11090117. 
  3. ↑ "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. PMID 11123360. 
  4. ↑ "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. doi:10.1038/sj.bjp.0705159. PMID 12684257. 
  5. ↑ "Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons". Neuroscience 106 (3): 579–87. 2001. doi:10.1016/S0306-4522(01)00297-4. PMID 11591458. 
  6. ↑ "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. doi:10.1124/jpet.106.103143. PMID 16803860. 
  7. ↑ "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. doi:10.1038/sj.bjp.0703923. PMID 11264235. 
  8. ↑ "Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats". Neuropharmacology 43 (2): 181–7. August 2002. doi:10.1016/S0028-3908(02)00082-5. PMID 12213272. 
  9. ↑ "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. PMID 11334240. 
  10. ↑ "The effect of the mGlu5 receptor antagonist MPEP in rodent tests of anxiety and cognition: a comparison". Psychopharmacology 179 (1): 218–29. April 2005. doi:10.1007/s00213-005-2211-9. PMID 15739074. 
  11. ↑ "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. doi:10.1007/s00213-005-2143-4. PMID 15682298. 
  12. ↑ "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. doi:10.1016/j.neuropharm.2004.09.010. PMID 15695156. 
  13. ↑ "Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the micro-opioid receptor". Neuropharmacology 56 (4): 768–78. March 2009. doi:10.1016/j.neuropharm.2008.12.010. PMID 19162047. 
  14. ↑ "Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP". CNS Drug Reviews 12 (2): 149–66. 2006. doi:10.1111/j.1527-3458.2006.00149.x. PMID 16958988. 
  15. ↑ "The mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice". Psychopharmacology 167 (3): 257–64. May 2003. doi:10.1007/s00213-003-1432-z. PMID 12682710. 
  16. ↑ "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. 2005. doi:10.1016/j.neuropharm.2005.06.007. PMID 16023685. 
  17. ↑ "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. doi:10.1016/j.ejphar.2004.07.056. PMID 15363959. 
  18. ↑ "The metabotropic glutamate receptor 5 antagonist MPEP decreased break points for nicotine, cocaine and food in rats". Psychopharmacology 179 (1): 255–61. April 2005. doi:10.1007/s00213-004-2070-9. PMID 15619120. 
  19. ↑ "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. doi:10.1097/FBP.0b013e3282f18d58. PMID 17989509. 
  20. ↑ "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. doi:10.1016/j.ejphar.2008.12.042. PMID 19210976. 
  21. ↑ "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. doi:10.1016/j.ejphar.2009.01.049. PMID 19326478. 



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