Wikipedia

MTEP

This is an old revision of this page, as edited by حسن علي البط (talk | contribs) at 06:34, 11 August 2010 (Adding category Category:Alkynes (using HotCat)). The present address (URL) is a permanent link to this revision, which may differ significantly from the current revision.

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
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

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. (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); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  2. ^ Iso Y, Grajkowska E, Wroblewski JT; et al. (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); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  3. ^ Kulkarni SS, Newman AH (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  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 (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. PMC 1576169. PMID 15821750. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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" (PDF). Pharmacol Rep. 58 (6): 846–58. PMID 17220542.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Szydlowska K, Kaminska B, Baude A, Parsons CG, Danysz W (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  8. ^ Pałucha A, Brański P, Szewczyk B, Wierońska JM, Kłak K, Pilc A (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  9. ^ Molina-Hernández M, Tellez-Alcántara NP, Pérez-García J, Olivera-Lopez JI, Jaramillo MT (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  10. ^ Li X, Need AB, Baez M, Witkin JM (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  11. ^ Belozertseva IV, Kos T, Popik P, Danysz W, Bespalov AY (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  12. ^ Zhu CZ, Wilson SG, Mikusa JP; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  13. ^ Varty GB, Grilli M, Forlani A; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  14. ^ Klodzinska A, Tatarczyńska E, Chojnacka-Wójcik E, Nowak G, Cosford ND, Pilc A (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  15. ^ Busse CS, Brodkin J, Tattersall D; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  16. ^ Pietraszek M, Sukhanov I, Maciejak P; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help); Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  17. ^ Stachowicz K, Gołembiowska K, Sowa M, Nowak G, Chojnacka-Wójcik E, Pilc A (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  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 (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}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  20. ^ Kotlinska J, Bochenski M (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  21. ^ Cowen MS, Djouma E, Lawrence AJ (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}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  22. ^ Cowen MS, Krstew E, Lawrence AJ (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}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  23. ^ Adams CL, Cowen MS, Short JL, Lawrence AJ (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}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  24. ^ Kotlinska J, Bochenski M (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  25. ^ Dravolina OA, Danysz W, Bespalov AY (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}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  26. ^ Palmatier MI, Liu X, Donny EC, Caggiula AR, Sved AF (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  27. ^ Gass JT, Osborne MP, Watson NL, Brown JL, Olive MF (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}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
  28. ^ Osborne MP, Olive MF (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. {{cite journal}}: Unknown parameter |month= ignored (help)
  29. ^ Martin-Fardon R, Baptista MA, Dayas CV, Weiss F (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. {{cite journal}}: Unknown parameter |month= ignored (help)CS1 maint: multiple names: authors list (link)
Retrieved from "https://en.wikipedia.org/w/index.php?title=MTEP&oldid=378317956"