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MTEP

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MTEP
Skeletal formula
Space-filling model
Identifiers
  • 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine
CAS Number
PubChemCID
IUPHAR/BPS
ChemSpider
CompTox Dashboard(EPA)
Chemical and physical data
FormulaC11H8N2S
Molar mass200.26g·mol−1
3D model (JSmol)
  • CC1=NC(=CS1)C#CC2=CN=CC=C2
  • InChI=1S/C11H8N2S/c1-9-13-11(8-14-9)5-4-10-3-2-6-12-7-10/h2-3,6-8H,1H3☒N
  • Key:NRBNGHCYDWUVLC-UHFFFAOYSA-N☒N
☒NcheckY(what is this?)(verify)

3-((2-Methyl-4-thiazolyl)ethynyl)pyridine(MTEP) is a research drug that was developed byMerck & Co.as a selectiveallostericantagonistof themetabotropic glutamate receptorsubtypemGluR5.Identified throughstructure-activity relationshipstudies on an older mGluR5 antagonistMPEP,[1]MTEP has subsequently itself acted as alead compoundfor newer and even more improved drugs.[2][3]

MTEP is both morepotentand moreselectivethanMPEPas a mGluR5 antagonist,[4]and produces similarneuroprotective,[5][6][7]antidepressant,[8][9][10][11]analgesic,[12][13]andanxiolyticeffects but with either similar or higherefficacydepending on the test used.[14][15][16][17]

MTEP also has similar efficacy to MPEP in reducing the symptoms ofmorphinewithdrawal,[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 ofnicotine,cocaineandmethamphetamine.[25][26][27][28][29]

See also[edit]

References[edit]

  1. ^Cosford ND, Tehrani L, Roppe J, Schweiger E, Smith ND, Anderson 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".Journal of Medicinal Chemistry.46(2): 204–206.doi:10.1021/jm025570j.PMID12519057.
  2. ^Iso Y, Grajkowska E, Wroblewski JT, Davis J, Goeders NE, Johnson KM, 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".Journal of Medicinal Chemistry.49(3): 1080–1100.doi:10.1021/jm050570f.PMID16451073.
  3. ^Kulkarni SS, Newman AH (June 2007)."Discovery of heterobicyclic templates for novel metabotropic glutamate receptor subtype 5 antagonists".Bioorganic & Medicinal Chemistry Letters.17(11): 2987–2991.doi:10.1016/j.bmcl.2007.03.066.PMC1973162.PMID17446071.
  4. ^Lea PM, Faden AI (2006)."Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP".CNS Drug Reviews.12(2): 149–166.doi:10.1111/j.1527-3458.2006.00149.x.PMC6494124.PMID16958988.
  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".British Journal of Pharmacology.145(4): 527–534.doi:10.1038/sj.bjp.0706219.PMC1576169.PMID15821750.
  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".Pharmacological Reports.58(6): 846–858.PMID17220542.
  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".European Journal of Pharmacology.554(1): 18–29.doi:10.1016/j.ejphar.2006.09.061.PMID17109843.
  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".Pharmacology, Biochemistry, and Behavior.81(4): 901–906.doi:10.1016/j.pbb.2005.06.015.PMID16040106.S2CID42920507.
  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".Progress in Neuro-Psychopharmacology & Biological Psychiatry.30(6): 1129–1135.doi:10.1016/j.pnpbp.2006.04.022.PMID16759778.S2CID45937198.
  10. ^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): 254–259.doi:10.1124/jpet.106.103143.PMID16803860.S2CID14632318.
  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".European Neuropsychopharmacology.17(3): 172–179.doi:10.1016/j.euroneuro.2006.03.002.PMID16630709.S2CID2420850.
  12. ^Zhu CZ, Wilson SG, Mikusa JP, Wismer CT, Gauvin DM, Lynch JJ, et al. (December 2004). "Assessing the role of metabotropic glutamate receptor 5 in multiple nociceptive modalities".European Journal of Pharmacology.506(2): 107–118.doi:10.1016/j.ejphar.2004.11.005.PMID15588730.
  13. ^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): 207–217.doi:10.1007/s00213-005-2143-4.PMID15682298.S2CID21807900.
  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): 342–350.doi:10.1016/j.neuropharm.2004.04.013.PMID15275823.S2CID54432014.
  15. ^Busse CS, Brodkin J, Tattersall D, Anderson JJ, Warren N, Tehrani L, 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): 1971–1979.doi:10.1038/sj.npp.1300540.PMID15305166.
  16. ^Pietraszek M, Sukhanov I, Maciejak P, Szyndler J, Gravius A, Wisłowska A, et al. (May 2005). "Anxiolytic-like effects of mGlu1 and mGlu5 receptor antagonists in rats".European Journal of Pharmacology.514(1): 25–34.doi:10.1016/j.ejphar.2005.03.028.PMID15878321.
  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): 741–748.doi:10.1016/j.neuropharm.2007.08.002.PMID17870136.S2CID24833690.
  18. ^Pałucha A, Brański P, Pilc A (2004)."Selective mGlu5 receptor antagonist MTEP attenuates naloxone-induced morphine withdrawal symptoms"(PDF).Polish Journal of Pharmacology.56(6): 863–866.PMID15662102.
  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): 173–180.doi:10.1016/j.neuropharm.2004.09.010.PMID15695156.S2CID13552709.
  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".European Journal of Pharmacology.558(1–3): 113–118.doi:10.1016/j.ejphar.2006.11.067.PMID17222405.
  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".The Journal of Pharmacology and Experimental Therapeutics.315(2): 590–600.doi:10.1124/jpet.105.090449.PMID16014750.S2CID11501029.
  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.190(1): 21–29.doi:10.1007/s00213-006-0583-0.PMID17096086.S2CID19977179.
  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".The International Journal of Neuropsychopharmacology.11(2): 229–241.doi:10.1017/S1461145707007845.hdl:11343/32923.PMID17517168.
  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".European Journal of Pharmacology.598(1–3): 57–63.doi:10.1016/j.ejphar.2008.09.026.PMID18838071.
  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.187(4): 397–404.doi:10.1007/s00213-006-0440-1.PMID16896963.S2CID21231365.
  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): 2139–2147.doi:10.1038/sj.npp.1301623.PMC2812904.PMID18046312.
  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): 820–833.doi:10.1038/npp.2008.140.PMC2669746.PMID18800068.
  28. ^Osborne MP, Olive MF (October 2008). "A role for mGluR5 receptors in intravenous methamphetamine self-administration".Annals of the New York Academy of Sciences.1139(1): 206–211.Bibcode:2008NYASA1139..206O.doi:10.1196/annals.1432.034.PMID18991866.S2CID207012906.
  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".The Journal of Pharmacology and Experimental Therapeutics.329(3): 1084–1090.doi:10.1124/jpet.109.151357.PMC2683783.PMID19258516.
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