Wikipedia

MTEP

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3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) is a research drug that was developed by Merck & Co. as a selective allosteric antagonist of the metabotropic glutamate receptor subtype mGluR5. Identified through structure-activity relationship studies on an older mGluR5 antagonist MPEP,[1] MTEP has subsequently itself acted as a lead compound for newer and even more improved drugs.[2][3]

MTEP
Skeletal formula
Space-filling model
Identifiers
  • 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC11H8N2S
Molar mass200.260 g/mol g·mol−1
3D model (JSmol)
  • CC1=NC(=CS1)C#CC2=CN=CC=C2
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MTEP is both more potent and more selective than MPEP as a mGluR5 antagonist,[4] and produces similar neuroprotective,[5][6][7] antidepressant,[8][9][10][11] analgesic,[12][13] and anxiolytic effects but with either similar or higher efficacy depending on the test used.[14][15][16][17]

MTEP also has similar efficacy to MPEP in reducing the symptoms of morphine withdrawal,[18][19][20] and has anti-addictive effects in a variety of animal models, both reducing ethanol self-administration,[21][22][23][24] and also decreasing the addictive effects of nicotine, cocaine and methamphetamine.[25][26][27][28][29]

References

  1. ^ Cosford ND, Tehrani L, Roppe J; et al. (January 2003). "3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]-pyridine: a potent and highly selective metabotropic glutamate subtype 5 receptor antagonist with anxiolytic activity". J. Med. Chem. 46 (2): 204–6. doi:10.1021/jm025570j. PMID 12519057. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  2. ^ Iso Y, Grajkowska E, Wroblewski JT; et al. (February 2006). "Synthesis and structure-activity relationships of 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine analogues as potent, noncompetitive metabotropic glutamate receptor subtype 5 antagonists; search for cocaine medications". J. Med. Chem. 49 (3): 1080–100. doi:10.1021/jm050570f. PMID 16451073. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
  3. ^ Kulkarni SS, Newman AH (June 2007). "Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists". Bioorg. Med. Chem. Lett. 17 (11): 2987–91. doi:10.1016/j.bmcl.2007.03.066. PMC 1973162. PMID 17446071.
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  18. ^ Pałucha A, Brański P, Pilc A (2004). "Selective mGlu5 receptor antagonist MTEP attenuates naloxone-induced morphine with-drawal symptoms" (PDF). Pol J Pharmacol. 56 (6): 863–6. PMID 15662102.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  20. ^ Kotlinska J, Bochenski M (March 2007). "Comparison of the effects of mGluR1 and mGluR5 antagonists on the expression of behavioral sensitization to the locomotor effect of morphine and the morphine withdrawal jumping in mice". Eur. J. Pharmacol. 558 (1–3): 113–8. doi:10.1016/j.ejphar.2006.11.067. PMID 17222405.
  21. ^ Cowen MS, Djouma E, Lawrence AJ (November 2005). "The metabotropic glutamate 5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine reduces ethanol self-administration in multiple strains of alcohol-preferring rats and regulates olfactory glutamatergic systems". J. Pharmacol. Exp. Ther. 315 (2): 590–600. doi:10.1124/jpet.105.090449. PMID 16014750.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Cowen MS, Krstew E, Lawrence AJ (January 2007). "Assessing appetitive and consummatory phases of ethanol self-administration in C57BL/6J mice under operant conditions: regulation by mGlu5 receptor antagonism". Psychopharmacology (Berl.). 190 (1): 21–9. doi:10.1007/s00213-006-0583-0. PMID 17096086.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  23. ^ Adams CL, Cowen MS, Short JL, Lawrence AJ (March 2008). "Combined antagonism of glutamate mGlu5 and adenosine A2A receptors interact to regulate alcohol-seeking in rats". Int. J. Neuropsychopharmacol. 11 (2): 229–41. doi:10.1017/S1461145707007845. PMID 17517168.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  24. ^ Kotlinska J, Bochenski M (November 2008). "The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats". Eur. J. Pharmacol. 598 (1–3): 57–63. doi:10.1016/j.ejphar.2008.09.026. PMID 18838071.
  25. ^ Dravolina OA, Danysz W, Bespalov AY (September 2006). "Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats". Psychopharmacology (Berl.). 187 (4): 397–404. doi:10.1007/s00213-006-0440-1. PMID 16896963.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  26. ^ Palmatier MI, Liu X, Donny EC, Caggiula AR, Sved AF (August 2008). "Metabotropic glutamate 5 receptor (mGluR5) antagonists decrease nicotine seeking, but do not affect the reinforcement enhancing effects of nicotine". Neuropsychopharmacology. 33 (9): 2139–47. doi:10.1038/sj.npp.1301623. PMC 2812904. PMID 18046312.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  27. ^ Gass JT, Osborne MP, Watson NL, Brown JL, Olive MF (March 2009). "mGluR5 antagonism attenuates methamphetamine reinforcement and prevents reinstatement of methamphetamine-seeking behavior in rats". Neuropsychopharmacology. 34 (4): 820–33. doi:10.1038/npp.2008.140. PMC 2669746. PMID 18800068.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  28. ^ Osborne MP, Olive MF (October 2008). "A role for mGluR5 receptors in intravenous methamphetamine self-administration". Ann. N. Y. Acad. Sci. 1139: 206–11. doi:10.1196/annals.1432.034. PMID 18991866.
  29. ^ Martin-Fardon R, Baptista MA, Dayas CV, Weiss F (June 2009). "Dissociation of the effects of MTEP [3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]piperidine] on conditioned reinstatement and reinforcement: comparison between cocaine and a conventional reinforcer". J. Pharmacol. Exp. Ther. 329 (3): 1084–90. doi:10.1124/jpet.109.151357. PMC 2683783. PMID 19258516.{{cite journal}}: CS1 maint: multiple names: authors list (link)
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