2-Methyl-6-(phenylethynyl)pyridine

Last updated
2-Methyl-6-(phenylethynyl)pyridine
Methylphenylethynylpyridine.svg
Identifiers
  • 2-Methyl-6-(phenylethynyl)pyridine
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C14H11N
Molar mass 193.249 g·mol−1
3D model (JSmol)
  • CC1=CC=CC(=N1)C#CC2=CC=CC=C2
  • InChI=1S/C14H11N.ClH/c1-12-6-5-9-14(15-12)11-10-13-7-3-2-4-8-13;/h2-9H,1H3;1H Yes check.svgY
  • Key:PKDHDJBNEKXCBI-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

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

Related Research Articles

<span class="mw-page-title-main">Metabotropic glutamate receptor</span> Type of glutamate receptor

The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter.

<span class="mw-page-title-main">NMDA receptor antagonist</span> Class of anesthetics

NMDA receptor antagonists are a class of drugs that work to antagonize, or inhibit the action of, the N-Methyl-D-aspartate receptor (NMDAR). They are commonly used as anesthetics for animals and humans; the state of anesthesia they induce is referred to as dissociative anesthesia.

<span class="mw-page-title-main">Fenobam</span> Chemical compound

Fenobam is an imidazole derivative developed by McNeil Laboratories in the late 1970s as a novel anxiolytic drug with an at-the-time-unidentified molecular target in the brain. Subsequently, it was determined that fenobam acts as a potent and selective negative allosteric modulator of the metabotropic glutamate receptor subtype mGluR5, and it has been used as a lead compound for the development of a range of newer mGluR5 antagonists.

<span class="mw-page-title-main">Metabotropic glutamate receptor 2</span> Mammalian protein found in humans

Metabotropic glutamate receptor 2 (mGluR2) is a protein that, in humans, is encoded by the GRM2 gene. mGluR2 is a G protein-coupled receptor (GPCR) that couples with the Gi alpha subunit. The receptor functions as an autoreceptor for glutamate, that upon activation, inhibits the emptying of vesicular contents at the presynaptic terminal of glutamatergic neurons.

<span class="mw-page-title-main">Metabotropic glutamate receptor 5</span> Mammalian protein found in humans

Metabotropic glutamate receptor 5 is an excitatory Gq-coupled G protein-coupled receptor predominantly expressed on the postsynaptic sites of neurons. In humans, it is encoded by the GRM5 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 7</span> Mammalian protein found in humans

Metabotropic glutamate receptor 7 is a protein that in humans is encoded by the GRM7 gene.

<span class="mw-page-title-main">Eglumetad</span> Chemical compound

Eglumetad is a research drug developed by Eli Lilly and Company, which is being investigated for its potential in the treatment of anxiety and drug addiction. It is a glutamate derived compound and its mode of action implies a novel mechanism.

<span class="mw-page-title-main">LY-341495</span> Chemical compound

LY-341495 is a research drug developed by the pharmaceutical company Eli Lilly, which acts as a potent and selective orthosteric antagonist for the group II metabotropic glutamate receptors (mGluR2/3).

<span class="mw-page-title-main">Tezampanel</span> Chemical compound

Tezampanel is a drug originally developed by Eli Lilly which acts as a competitive antagonist of the AMPA and kainate subtypes of the ionotropic glutamate receptor family, with selectivity for the GluR5 subtype of the kainate receptor. It has neuroprotective and anticonvulsant properties, the former of which may, at least in part, occur via blockade of calcium uptake into neurons.

<span class="mw-page-title-main">AMN082</span> Chemical compound

AMN082 is a selective metabotropic glutamate receptor 7 (mGluR7) allosteric agonist. It mimics the effect of glutamate. AMN082 is the first selective mGluR7 agonist and has expanded the potential array of research opportunities on the effects of mGluR7 in the central nervous system.

<span class="mw-page-title-main">MTEP</span> Chemical compound

3-( 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, MTEP has subsequently itself acted as a lead compound for newer and even more improved drugs.

<span class="mw-page-title-main">EGLU</span> Chemical compound

EGLU is a drug that is used in neuroscience research. It was one of the first compounds found that acts as a selective antagonist for the group II metabotropic glutamate receptors (mGluR2/3), and so has been useful in the characterization and study of this receptor subfamily.

<span class="mw-page-title-main">PHCCC</span>

PHCCC is a research drug which acts as a glutamate receptor ligand, particularly being a positive allosteric modulator at the mGluR4 subtype, as well as an agonist at mGluR6. It has anxiolytic effects in animal studies. PHCCC and similar drugs have been suggested as novel treatments for Parkinson's disease.

<span class="mw-page-title-main">SIB-1757</span> Chemical compound

SIB-1757 is a drug used in scientific research which was one of the first compounds developed that acts as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. It has anti-hyperalgesia effects in animals. SIB-1757 along with other mGluR5 antagonists has been shown to have neuroprotective and hepatoprotective effects, and it is also used to study the role of the mGluR5 receptor in brain development.

<span class="mw-page-title-main">SIB-1893</span> Chemical compound

SIB-1893 is a drug used in scientific research which was one of the first compounds developed that acts as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. It has anticonvulsant and neuroprotective effects, and reduces glutamate release. It has also been found to act as a positive allosteric modulator of mGluR4.

<span class="mw-page-title-main">CDPPB</span> Chemical compound

CDPPB is a drug used in scientific research which acts as a positive allosteric modulator selective for the metabotropic glutamate receptor subtype mGluR5. It has antipsychotic effects in animal models, and mGluR5 modulators are under investigation as potential drugs for the treatment of schizophrenia, as well as other applications.

<span class="mw-page-title-main">LY-379,268</span> Chemical compound

LY-379,268 is a drug that is used in neuroscience research, which acts as a potent and selective agonist for the group II metabotropic glutamate receptors (mGluR2/3).

<span class="mw-page-title-main">LY-487,379</span> Chemical compound

LY-487,379 is a drug used in scientific research that acts as a selective positive allosteric modulator for the metabotropic glutamate receptor group II subtype mGluR2. It is used to study the structure and function of this receptor subtype, and LY-487,379 along with various other mGluR2/3 agonists and positive modulators are being investigated as possible antipsychotic and anxiolytic drugs.

<span class="mw-page-title-main">MGS-0039</span> Chemical compound

MGS-0039 is a drug that is used in neuroscientific research, which acts as a potent and selective antagonist for group II of the metabotropic glutamate receptors (mGluR2/3). It produces antidepressant and anxiolytic effects in animal studies, and has been shown to boost release of dopamine and serotonin in specific brain areas. Research has suggested this may occur through a similar mechanism as that suggested for the similarly glutamatergic drug ketamine.

<span class="mw-page-title-main">GRN-529</span> Chemical compound

GRN-529 is a drug that was developed by Wyeth as a negative allosteric modulator of the metabotropic glutamate receptor 5 (mGluR5).

References

  1. ↑ Micheli F (November 2000). "Methylphenylethynylpyridine (MPEP) Novartis". Current Opinion in Investigational Drugs. 1 (3): 355–9. PMID   11249719.
  2. ↑ O'Leary DM, Movsesyan V, Vicini S, Faden AI (December 2000). "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. doi:10.1038/sj.bjp.0703715. PMC   1572472 . PMID   11090117.
  3. ↑ Movsesyan VA, O'Leary DM, Fan L, Bao W, Mullins PG, Knoblach SM, Faden AI (January 2001). "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. PMID   11123360.
  4. ↑ Mathiesen JM, Svendsen N, Bräuner-Osborne H, Thomsen C, Ramirez MT (March 2003). "Positive allosteric modulation of the human metabotropic glutamate receptor 4 (hmGluR4) by SIB-1893 and MPEP". British Journal of Pharmacology. 138 (6): 1026–30. doi:10.1038/sj.bjp.0705159. PMC   1573757 . PMID   12684257.
  5. ↑ Pisani A, Gubellini P, Bonsi P, Conquet F, Picconi B, Centonze D, et al. (2001). "Metabotropic glutamate receptor 5 mediates the potentiation of N-methyl-D-aspartate responses in medium spiny striatal neurons". Neuroscience. 106 (3): 579–87. doi:10.1016/S0306-4522(01)00297-4. PMID   11591458. S2CID   38753726.
  6. ↑ 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): 254–9. doi:10.1124/jpet.106.103143. PMID   16803860. S2CID   14632318.
  7. ↑ Tatarczyńska E, Klodzińska A, Chojnacka-Wójcik E, Palucha A, Gasparini F, Kuhn R, Pilc A (April 2001). "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. doi:10.1038/sj.bjp.0703923. PMC   1572682 . PMID   11264235.
  8. ↑ Pilc A, Kłodzińska A, Brański P, Nowak G, Pałucha A, Szewczyk B, et al. (August 2002). "Multiple MPEP administrations evoke anxiolytic- and antidepressant-like effects in rats". Neuropharmacology. 43 (2): 181–7. doi:10.1016/S0028-3908(02)00082-5. PMID   12213272. S2CID   23177632.
  9. ↑ Kłodzińska A, Tatarczyńska E, Chojnacka-Wójcik E, Pilc A (2000). "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. PMID   11334240.
  10. ↑ Ballard TM, Woolley ML, Prinssen E, Huwyler J, Porter R, Spooren W (April 2005). "The effect of the mGlu5 receptor antagonist MPEP in rodent tests of anxiety and cognition: a comparison". Psychopharmacology. 179 (1): 218–29. doi:10.1007/s00213-005-2211-9. PMID   15739074. S2CID   25136496.
  11. ↑ 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): 207–17. doi:10.1007/s00213-005-2143-4. PMID   15682298. S2CID   21807900.
  12. ↑ 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. S2CID   13552709.
  13. ↑ Schröder H, Wu DF, Seifert A, Rankovic M, Schulz S, Höllt V, Koch T (March 2009). "Allosteric modulation of metabotropic glutamate receptor 5 affects phosphorylation, internalization, and desensitization of the micro-opioid receptor". Neuropharmacology. 56 (4): 768–78. doi:10.1016/j.neuropharm.2008.12.010. PMID   19162047. S2CID   41530896.
  14. ↑ Lea PM, Faden AI (2006). "Metabotropic glutamate receptor subtype 5 antagonists MPEP and MTEP". CNS Drug Reviews. 12 (2): 149–66. doi:10.1111/j.1527-3458.2006.00149.x. PMC   6494124 . PMID   16958988.
  15. ↑ Paterson NE, Semenova S, Gasparini F, Markou A (May 2003). "The mGluR5 antagonist MPEP decreased nicotine self-administration in rats and mice". Psychopharmacology. 167 (3): 257–64. doi:10.1007/s00213-003-1432-z. PMID   12682710. S2CID   40627145.
  16. ↑ Bespalov AY, Dravolina OA, Sukhanov I, Zakharova E, Blokhina E, Zvartau E, et al. (2005). "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. doi:10.1016/j.neuropharm.2005.06.007. PMID   16023685. S2CID   37283433.
  17. ↑ Tessari M, Pilla M, Andreoli M, Hutcheson DM, Heidbreder CA (September 2004). "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. doi:10.1016/j.ejphar.2004.07.056. PMID   15363959.
  18. ↑ Paterson NE, Markou A (April 2005). "The metabotropic glutamate receptor 5 antagonist MPEP decreased break points for nicotine, cocaine and food in rats". Psychopharmacology. 179 (1): 255–61. doi:10.1007/s00213-004-2070-9. PMID   15619120. S2CID   24096619.
  19. ↑ van der Kam EL, de Vry J, Tzschentke TM (December 2007). "Effect of 2-methyl-6-(phenylethynyl) pyridine on intravenous self-administration of ketamine and heroin in the rat". Behavioural Pharmacology. 18 (8): 717–24. doi:10.1097/FBP.0b013e3282f18d58. PMID   17989509. S2CID   24990842.
  20. ↑ van der Kam EL, De Vry J, Tzschentke TM (March 2009). "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. doi:10.1016/j.ejphar.2008.12.042. PMID   19210976.
  21. ↑ van der Kam EL, De Vry J, Tzschentke TM (April 2009). "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. doi:10.1016/j.ejphar.2009.01.049. PMID   19326478.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.