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MTEP
Systematic (IUPAC) name
3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine
Identifiers
CAS number 329205-68-7
ATC code  ?
PubChem 9794218
Chemical data
Formula C 11H8N2S 
Mol. mass 200.260 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.  ?
Legal status
Routes  ?

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 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.  
  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.  
  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. PMID 17446071.  
  4. ^ Lea PM, Faden AI (2006). "Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP". CNS Drug Rev 12 (2): 149–66. doi:10.1111/j.1527-3458.2006.00149.x. PMID 16958988.  
  5. ^ Lea PM, Movsesyan VA, Faden AI (June 2005). "Neuroprotective activity of the mGluR5 antagonists MPEP and MTEP against acute excitotoxicity differs and does not reflect actions at mGluR5 receptors". Br. J. Pharmacol. 145 (4): 527–34. doi:10.1038/sj.bjp.0706219. PMID 15821750.  
  6. ^ Domin H, Kajta M, Smiałowska M (2006). "Neuroprotective effects of MTEP, a selective mGluR5 antagonists and neuropeptide Y on the kainate-induced toxicity in primary neuronal cultures". Pharmacol Rep 58 (6): 846–58. PMID 17220542. http://www.if-pan.krakow.pl/pjp/pdf/2006/6_846.pdf.  
  7. ^ Szydlowska K, Kaminska B, Baude A, Parsons CG, Danysz W (January 2007). "Neuroprotective activity of selective mGlu1 and mGlu5 antagonists in vitro and in vivo". Eur. J. Pharmacol. 554 (1): 18–29. doi:10.1016/j.ejphar.2006.09.061. PMID 17109843.  
  8. ^ Pałucha A, Brański P, Szewczyk B, Wierońska JM, Kłak K, Pilc A (August 2005). "Potential antidepressant-like effect of MTEP, a potent and highly selective mGluR5 antagonist". Pharmacol. Biochem. Behav. 81 (4): 901–6. doi:10.1016/j.pbb.2005.06.015. PMID 16040106.  
  9. ^ Molina-Hernández M, Tellez-Alcántara NP, Pérez-García J, Olivera-Lopez JI, Jaramillo MT (August 2006). "Antidepressant-like and anxiolytic-like actions of the mGlu5 receptor antagonist MTEP, microinjected into lateral septal nuclei of male Wistar rats". Prog. Neuropsychopharmacol. Biol. Psychiatry 30 (6): 1129–35. doi:10.1016/j.pnpbp.2006.04.022. PMID 16759778.  
  10. ^ Li X, Need AB, Baez M, Witkin JM (October 2006). "Metabotropic glutamate 5 receptor antagonism is associated with antidepressant-like effects in mice". J. Pharmacol. Exp. Ther. 319 (1): 254–9. doi:10.1124/jpet.106.103143. PMID 16803860.  
  11. ^ Belozertseva IV, Kos T, Popik P, Danysz W, Bespalov AY (February 2007). "Antidepressant-like effects of mGluR1 and mGluR5 antagonists in the rat forced swim and the mouse tail suspension tests". Eur Neuropsychopharmacol 17 (3): 172–9. doi:10.1016/j.euroneuro.2006.03.002. PMID 16630709.  
  12. ^ Zhu CZ, Wilson SG, Mikusa JP, et al. (December 2004). "Assessing the role of metabotropic glutamate receptor 5 in multiple nociceptive modalities". Eur. J. Pharmacol. 506 (2): 107–18. doi:10.1016/j.ejphar.2004.11.005. PMID 15588730.  
  13. ^ Varty GB, Grilli M, Forlani A, 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 (Berl.) 179 (1): 207–17. doi:10.1007/s00213-005-2143-4. PMID 15682298.  
  14. ^ Klodzinska A, Tatarczyńska E, Chojnacka-Wójcik E, Nowak G, Cosford ND, Pilc A (September 2004). "Anxiolytic-like effects of MTEP, a potent and selective mGlu5 receptor agonist does not involve GABA(A) signaling". Neuropharmacology 47 (3): 342–50. doi:10.1016/j.neuropharm.2004.04.013. PMID 15275823.  
  15. ^ Busse CS, Brodkin J, Tattersall D, et al. (November 2004). "The behavioral profile of the potent and selective mGlu5 receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) in rodent models of anxiety". Neuropsychopharmacology 29 (11): 1971–9. doi:10.1038/sj.npp.1300540. PMID 15305166.  
  16. ^ Pietraszek M, Sukhanov I, Maciejak P, et al. (May 2005). "Anxiolytic-like effects of mGlu1 and mGlu5 receptor antagonists in rats". Eur. J. Pharmacol. 514 (1): 25–34. doi:10.1016/j.ejphar.2005.03.028. PMID 15878321.  
  17. ^ Stachowicz K, Gołembiowska K, Sowa M, Nowak G, Chojnacka-Wójcik E, Pilc A (November 2007). "Anxiolytic-like action of MTEP expressed in the conflict drinking Vogel test in rats is serotonin dependent". Neuropharmacology 53 (6): 741–8. doi:10.1016/j.neuropharm.2007.08.002. PMID 17870136.  
  18. ^ Pałucha A, Brański P, Pilc A (2004). "Selective mGlu5 receptor antagonist MTEP attenuates naloxone-induced morphine with-drawal symptoms". Pol J Pharmacol 56 (6): 863–6. PMID 15662102. http://www.if-pan.krakow.pl/pjp/pdf/2004/6_863.pdf.  
  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.  
  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.  
  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.  
  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.  
  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.  
  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. PMID 18046312.  
  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. PMID 18800068.  
  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. PMID 19258516.  







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