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).[1][2][3][4]
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.[18]
^ Ornstein PL, Bleisch TJ, Arnold MB, Kennedy JH, Wright RA, Johnson BG, Tizzano JP, Helton DR, Kallman MJ, Schoepp DD, Hérin M (January 1998). "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. 41 (3): 358–78. doi:10.1021/jm970498o. PMID9464367.
^Kingston AE, Ornstein PL, Wright RA, Johnson BG, Mayne NG, Burnett JP, Belagaje R, Wu S, Schoepp DD (1998). "LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors". Neuropharmacology. 37 (1): 1–12. doi:10.1016/s0028-3908(97)00191-3. PMID9680254. S2CID27186381.
^Fitzjohn SM, Bortolotto ZA, Palmer MJ, Doherty AJ, Ornstein PL, Schoepp DD, Kingston AE, Lodge D, Collingridge GL (December 1998). "The potent mGlu receptor antagonist LY341495 identifies roles for both cloned and novel mGlu receptors in hippocampal synaptic plasticity". Neuropharmacology. 37 (12): 1445–58. doi:10.1016/s0028-3908(98)00145-2. PMID9886667. S2CID26102806.
^Johnson BG, Wright RA, Arnold MB, Wheeler WJ, Ornstein PL, Schoepp DD (October 1999). "[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. 38 (10): 1519–29. doi:10.1016/s0028-3908(99)00053-2. PMID10530814. S2CID36767061.
^Pilc A, Chaki S, Nowak G, Witkin JM (March 2008). "Mood disorders: regulation by metabotropic glutamate receptors". Biochemical Pharmacology. 75 (5): 997–1006. doi:10.1016/j.bcp.2007.09.021. PMID18164691.
^Matrisciano F, Panaccione I, Zusso M, Giusti P, Tatarelli R, Iacovelli L, Mathé AA, Gruber SH, Nicoletti F, Girardi P (August 2007). "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. 12 (8): 704–6. doi:10.1038/sj.mp.4002005. PMID17653204. S2CID7906551.
^Koike H, Chaki S (September 2014). "Requirement of AMPA receptor stimulation for the sustained antidepressant activity of ketamine and LY341495 during the forced swim test in rats". Behavioural Brain Research. 271: 111–5. doi:10.1016/j.bbr.2014.05.065. PMID24909673. S2CID19982406.
^Benneyworth MA, Xiang Z, Smith RL, Garcia EE, Conn PJ, Sanders-Bush E (August 2007). "A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis". Molecular Pharmacology. 72 (2): 477–84. doi:10.1124/mol.107.035170. PMID17526600. S2CID3097502.
^Moreno JL, González-Maeso J (2018). "Crosstalk Between 5-HT2A and mGlu2 Receptors: Implications in Schizophrenia and Its Treatment". 5-HT2A Receptors in the Central Nervous System. The Receptors. Vol. 32. pp. 147–189. doi:10.1007/978-3-319-70474-6_7. ISBN978-3-319-70472-2.
^Fischer BD, Miller LL, Henry FE, Picker MJ, Dykstra LA (June 2008). "Increased efficacy of micro-opioid agonist-induced antinociception by metabotropic glutamate receptor antagonists in C57BL/6 mice: comparison with (-)-6-phosphonomethyl-deca-hydroisoquinoline-3-carboxylic acid (LY235959)". Psychopharmacology. 198 (2): 271–8. doi:10.1007/s00213-008-1130-y. PMID18392754. S2CID24658889.
^Fischer BD, Zimmerman EI, Picker MJ, Dykstra LA (February 2008). "Morphine in combination with metabotropic glutamate receptor antagonists on schedule-controlled responding and thermal nociception". The Journal of Pharmacology and Experimental Therapeutics. 324 (2): 732–9. doi:10.1124/jpet.107.131417. PMID17982001. S2CID12497552.
^O'Neill MF, Heron-Maxwell C, Conway MW, Monn JA, Ornstein P (October 2003). "Group II metabotropic glutamate receptor antagonists LY341495 and LY366457 increase locomotor activity in mice". Neuropharmacology. 45 (5): 565–74. doi:10.1016/S0028-3908(03)00232-6. PMID12941370. S2CID22992987.
^Chi H, Jang JK, Kim JH, Vezina P (October 2006). "Blockade of group II metabotropic glutamate receptors in the nucleus accumbens produces hyperlocomotion in rats previously exposed to amphetamine". Neuropharmacology. 51 (5): 986–92. doi:10.1016/j.neuropharm.2006.06.008. PMID16901517. S2CID22562384.
^Yoon HS, Jang JK, Kim JH (September 2008). "Blockade of group II metabotropic glutamate receptors produces hyper-locomotion in cocaine pre-exposed rats by interactions with dopamine receptors". Neuropharmacology. 55 (4): 555–9. doi:10.1016/j.neuropharm.2008.07.012. PMID18675831. S2CID12164609.
^Sakagami K, Yasuhara A, Chaki S, Yoshikawa R, Kawakita Y, Saito A, Taguchi T, Nakazato A (April 2008). "Synthesis, in vitro pharmacology, and pharmacokinetic profiles of 2-[1-amino-1-carboxy-2-(9H-xanthen-9-yl)-ethyl]-1-fluorocyclopropanecarboxylic acid and its 6-heptyl ester, a potent mGluR2 antagonist". Bioorganic & Medicinal Chemistry. 16 (8): 4359–66. doi:10.1016/j.bmc.2008.02.066. PMID18348906.