LSP2-9166

Last updated
LSP2-9166
LSP2-9166 structure.png
Identifiers
  • (2S)-2-amino-4-[[[4-(carboxymethoxy)-3-(trifluoromethoxy)phenyl]-hydroxymethyl]-hydroxyphosphoryl]butanoic acid
PubChem CID
ChemSpider
Chemical and physical data
Formula C14H17F3NO9P
Molar mass 431.257 g·mol−1
3D model (JSmol)
  • C1=CC(=C(C=C1C(O)P(=O)(CC[C@@H](C(=O)O)N)O)OC(F)(F)F)OCC(=O)O
  • InChI=1S/C14H17F3NO9P/c15-14(16,17)27-10-5-7(1-2-9(10)26-6-11(19)20)13(23)28(24,25)4-3-8(18)12(21)22/h1-2,5,8,13,23H,3-4,6,18H2,(H,19,20)(H,21,22)(H,24,25)/t8-,13?/m0/s1
  • Key:NTRJZUQSNSIKLO-OADYLZGLSA-N

LSP2-9166 is a drug which acts as a selective agonist for the group III metabotropic glutamate receptors, with a reasonably potent EC50 of 70nM at mGluR4 and 220nM at mGluR7, and weaker activity of 1380nM at mGluR6 and 4800nM at mGluR8. [1] It has anticonvulsant effects in animal studies, [2] [3] and reduces self-administration of various addictive drugs. [4] [5] [6]


Related Research Articles

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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">Metabotropic glutamate receptor 1</span> Mammalian protein found in humans

The glutamate receptor, metabotropic 1, also known as GRM1, is a human gene which encodes the metabotropic glutamate receptor 1 (mGluR1) protein.

<span class="mw-page-title-main">Metabotropic glutamate receptor 4</span> Mammalian protein found in humans

Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the GRM4 gene.

<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">Metabotropic glutamate receptor 8</span> Mammalian protein found in humans

Metabotropic glutamate receptor 8 is a protein that in humans is encoded by the GRM8 gene.

<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">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">2-Methyl-6-(phenylethynyl)pyridine</span> Chemical compound

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. 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, and as a positive allosteric modulator of another subtype mGlu4, and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons. It was also shown to produce antidepressant and anxiolytic effects in animals, and to reduce the effects of morphine withdrawal, most likely due to direct interaction between mGluR5 and the μ-opioid receptor.

<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">Pomaglumetad</span> Drug, used as a treatment for schizophrenia

Pomaglumetad (LY-404,039) is an amino acid analog drug that acts as a highly selective agonist for the metabotropic glutamate receptor group II subtypes mGluR2 and mGluR3. Pharmacological research has focused on its potential antipsychotic and anxiolytic effects. Pomaglumetad is intended as a treatment for schizophrenia and other psychotic and anxiety disorders by modulating glutamatergic activity and reducing presynaptic release of glutamate at synapses in limbic and forebrain areas relevant to these disorders. Human studies investigating therapeutic use of pomaglumetad have focused on the prodrug LY-2140023, a methionine amide of pomaglumetad (also called pomaglumetad methionil) since pomaglumetad exhibits low oral absorption and bioavailability in humans.

<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">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">L-AP4</span> Chemical compound

L-AP4 (L-2-amino-4-phosphonobutyric acid) is a drug used in scientific research, which acts as a group-selective agonist for the group III metabotropic glutamate receptors (mGluR4/6/7/8). It was the first ligand found to act as an agonist selective for this group of mGlu receptors, but does not show selectivity between the different mGluR Group III subtypes. It is widely used in the study of this receptor family and their various functions.

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

DCPG ((S)-3,4-DCPG) is a drug used in scientific research, which acts as a potent and subtype-selective agonist for the metabotropic glutamate receptor mGluR8. It has anticonvulsant effects in animal studies, and has also been investigated as a possible treatment for hyperalgesia.

<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">Chlorohydroxyphenylglycine</span> Chemical compound

2-Chloro-5-hydroxyphenylglycine or CHPG is an agonist of the metabotropic glutamate receptors, specific for mGluR5.

<span class="mw-page-title-main">AZD9272</span> Medication

AZD 9272 is a drug which acts as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. It was unsuccessful in human trials as an analgesic, but continues to be widely used in research especially as its radiolabelled forms.

<span class="mw-page-title-main">AZ12216052</span> Chemical compound

AZ-12216052 is a drug which acts as a potent and selective positive allosteric modulator of the metabotropic glutamate receptor 8, and is used for research into the role of this receptor subtype in various processes including anxiety and neuropathic pain.

<span class="mw-page-title-main">XAP044</span> Chemical compound

XAP044 is a drug which acts as a potent and selective antagonist of the metabotropic glutamate receptor 7 (mGluR7). It inhibits long-term potentiation in the amygdala and inhibits responses associated with stress and anxiety in animal models, as well as being used to study the role of mGluR7 in various other processes.

References

  1. ↑ Acher FC, Cabayé A, Eshak F, Goupil-Lamy A, Pin JP (February 2022). "Metabotropic glutamate receptor orthosteric ligands and their binding sites". Neuropharmacology. 204: 108886. doi: 10.1016/j.neuropharm.2021.108886 . PMID   34813860.
  2. ↑ Girard B, Tuduri P, Moreno MP, Sakkaki S, Barboux C, Bouschet T, et al. (September 2019). "The mGlu7 receptor provides protective effects against epileptogenesis and epileptic seizures". Neurobiology of Disease. 129: 13–28. doi: 10.1016/j.nbd.2019.04.016 . PMID   31051234.
  3. ↑ Kovalenko AA, Zakharova MV, Schwarz AP, Dyomina AV, Zubareva OE, Zaitsev AV (March 2022). "Changes in Metabotropic Glutamate Receptor Gene Expression in Rat Brain in a Lithium-Pilocarpine Model of Temporal Lobe Epilepsy". International Journal of Molecular Sciences. 23 (5): 2752. doi: 10.3390/ijms23052752 . PMC   8910969 . PMID   35269897.
  4. ↑ Hajasova Z, Canestrelli C, Acher F, Noble F, Marie N (March 2018). "Role of mGlu7 receptor in morphine rewarding effects is uncovered by a novel orthosteric agonist". Neuropharmacology. 131: 424–430. doi:10.1016/j.neuropharm.2018.01.002. PMID   29307544. S2CID   3391450.
  5. ↑ Lebourgeois S, Vilpoux C, Jeanblanc J, Acher F, Marie N, Noble F, Naassila M (May 2018). "Pharmacological activation of mGlu4 and mGlu7 receptors, by LSP2-9166, reduces ethanol consumption and relapse in rat". Neuropharmacology. 133: 163–170. doi:10.1016/j.neuropharm.2018.01.031. PMID   29378211. S2CID   3959313.
  6. ↑ De Sa Nogueira D, Bourdy R, Filliol D, Quessada C, McCort-Tranchepain I, Acher F, et al. (November 2021). "LSP2-9166, an orthosteric mGlu4 and mGlu7 receptor agonist, reduces cocaine self-administration under a progressive ratio schedule in rats" (PDF). Neuroscience Letters. 764: 135603. doi:10.1016/j.neulet.2020.135603. PMID   33387661. S2CID   229724310.


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