LY-341,495

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LY-341,495
LY-341,495.svg
Systematic (IUPAC) name
2-[(1S,2S)-2-carboxycyclopropyl]-3-(9H-xanthen-9-yl)-D-alanine
Identifiers
CAS Number 201943-63-7 YesY
ChemSpider 7995676 N
Synonyms (2S)-2-Amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl)propanoic acid
Chemical data
Formula C20H19NO5
Molecular mass 353.37 g/mol
  • C1[C@@H]([C@H]1[C@@](CC2C3=CC=CC=C3OC4=CC=CC=C24)(C(=O)O)N)C(=O)O
  • InChI=1S/C20H19NO5/c21-20(19(24)25,15-9-13(15)18(22)23)10-14-11-5-1-3-7-16(11)26-17-8-4-2-6-12(14)17/h1-8,13-15H,9-10,21H2,(H,22,23)(H,24,25)/t13-,15-,20-/m0/s1 N
  • Key:VLZBRVJVCCNPRJ-KPHUOKFYSA-N N
 NYesY (what is this?)  (verify)

LY-341,495 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).[1][2][3][4]

It is used in scientific research in several different areas, showing antidepressant effects in animal models,[5][6][7] increasing the behavioural effects of hallucinogenic drugs in animal tests,[8][9][10] and increasing the analgesic effects of μ-opioid agonists,[11][12] as well as modulating dopamine receptor function.[13][14][15]

The 1-fluorocyclopropane analog has a superior pharmacokinetic profile and similar mGluR2/3 affinity, and making a prodrug from this with the heptyl ester increases bioavailability still further.[16]

1-fluoro-LY-341,495 heptyl ester

See also

References

  1. ↑ Ornstein PL, Bleisch TJ, Arnold MB, Kennedy JH, Wright RA, Johnson BG, Tizzano JP, Helton DR, Kallman MJ, Schoepp DD, Hérin M. 2-substituted (2SR)-2-amino-2-((1SR,2SR)-2-carboxycycloprop-1-yl)glycines as potent and selective antagonists of group II metabotropic glutamate receptors. 2. Effects of aromatic substitution, pharmacological characterization, and bioavailability. Journal of Medicinal Chemistry. 1998 Jan 29;41(3):358-78. PMID 9464367.
  2. ↑ Kingston AE, Ornstein PL, Wright RA, Johnson BG, Mayne NG, Burnett JP, Belagaje R, Wu S, Schoepp DD. LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors. Neuropharmacology. 1998;37(1):1-12. PMID 9680254 .
  3. ↑ Fitzjohn SM, Bortolotto ZA, Palmer MJ, Doherty AJ, Ornstein PL, Schoepp DD, Kingston AE, Lodge D, Collingridge GL. The potent mGlu receptor antagonist LY341495 identifies roles for both cloned and novel mGlu receptors in hippocampal synaptic plasticity. Neuropharmacology. 1998 Dec;37(12):1445-58. PMID 9886667
  4. ↑ Johnson BG, Wright RA, Arnold MB, Wheeler WJ, Ornstein PL, Schoepp DD. [3H]-LY341495 as a novel antagonist radioligand for group II metabotropic glutamate (mGlu) receptors: characterization of binding to membranes of mGlu receptor subtype expressing cells. Neuropharmacology. 1999 Oct;38(10):1519-29. PMID 10530814.
  5. ↑ Pilc A, Chaki S, Nowak G, Witkin JM. Mood disorders: regulation by metabotropic glutamate receptors. Biochemical Pharmacology. 2008 Mar 1;75(5):997-1006. PMID 18164691
  6. ↑ Matrisciano F, Panaccione I, Zusso M, Giusti P, Tatarelli R, Iacovelli L, Mathé AA, Gruber SH, Nicoletti F, Girardi P. Group-II metabotropic glutamate receptor ligands as adjunctive drugs in the treatment of depression: a new strategy to shorten the latency of antidepressant medication? Molecular Psychiatry. 2007 Aug;12(8):704-6. PMID 17653204
  7. ↑ Koike H, Chaki S. Requirement of AMPA receptor stimulation for the sustained antidepressant activity of ketamine and LY341495 during the forced swim test in rats. Behavioral Brain Research. 2014 Sep 1;271:111-5. doi: 10.1016/j.bbr.2014.05.065. PMID 24909673
  8. ↑ Gewirtz JC, Marek GJ. Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors. Neuropsychopharmacology. 2000 Nov;23(5):569-76. PMID 11027922
  9. ↑ Benneyworth MA, Xiang Z, Smith RL, Garcia EE, Conn PJ, Sanders-Bush E. A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis. Molecular Pharmacology. 2007 Aug;72(2):477-84. PMID 17526600
  10. ↑ Carbonaro TM, Eshleman AJ, Forster MJ, Cheng K, Rice KC, Gatch MB. The role of 5-HT2A, 5-HT 2C and mGlu2 receptors in the behavioral effects of tryptamine hallucinogens N,N-dimethyltryptamine and N,N-diisopropyltryptamine in rats and mice. Psychopharmacology (Berlin). 2014 Jul 3. PMID 24985890
  11. ↑ Fischer BD, Miller LL, Henry FE, Picker MJ, Dykstra LA. Increased efficacy of mu-opioid agonist-induced antinociception by metabotropic glutamate receptor antagonists in C57BL/6 mice: comparison with (−)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959). Psychopharmacology (Berlin). 2008 Apr 8; PMID 18392754
  12. ↑ Fischer BD, Zimmerman EI, Picker MJ, Dykstra LA. Morphine in combination with metabotropic glutamate receptor antagonists on schedule-controlled responding and thermal nociception. Journal of Pharmacology and Experimental Therapeutics. 2008 Feb;324(2):732-9. PMID 17982001
  13. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.


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