Википедија

LY-341,495

LY-341,495 je istraživački lek koji deluje kao potentan i selektivan ortosterni antagonist za grupu II metabotropnih glutamatnih receptora (mGluR2/3).[1][2][3][4]

LY-341,495
IUPAC ime
2-[(1S,2S)-2-karboksiciklopropil]-3-(9H-ksanten-9-il)-D-alanine
Identifikatori
CAS broj201943-63-7 ДаY
ATC kodnone
Sinonimi(2S)-2-Amino-2-[(1S,2S)-2-karboksicikloprop-1-il]-3-(ksant-9-il)propanoinska kiselina
Hemijski podaci
FormulaC20H19NO5
Molarna masa353,37 g/mol

On se koristi u nekoliko oblasti naučnih istraživanja. On pokazuje antidepresivno dejstvo u životinjskim modelima,[5][6] gde povećava dejstvo halucinogenih lekova,[7][8] i povećava analgetičko dejstvo μ-opioidnih agonista,[9][10] kao i modulaciju funkcija dopaminskog receptora.[11][12][13]

1-fluorociklopropanski analog ima superiorni farmakokinetički profil i sličan mGluR2/3 afinitet. Prolek u obliku heptil estra ima poboljšanu bioadostupnost.[14]

1-fluoro-LY-341,495 heptil estar

Reference уреди

  1. ^ Ornstein PL, Bleisch TJ, Arnold MB, Kennedy JH, Wright RA, Johnson BG, Tizzano JP, Helton DR, Kallman MJ, Schoepp DD, Hérin M. Journal of Medicinal Chemistry. 1998 Jan 29; . „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.”. 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. Neuropharmacology. 1998; . „LY341495 is a nanomolar potent and selective antagonist of group II metabotropic glutamate receptors.”. 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. Neuropharmacology. 1998 Dec; . „The potent mGlu receptor antagonist LY341495 identifies roles for both cloned and novel mGlu receptors in hippocampal synaptic plasticity”. 37 (12): 1445—58. PMID 9886667. 
  4. ^ Johnson BG, Wright RA, Arnold MB, Wheeler WJ, Ornstein PL, Schoepp DD. Neuropharmacology. 1999 Oct; . „[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.”. 38 (10): 1519—29. PMID 10530814. .
  5. ^ Pilc A, Chaki S, Nowak G, Witkin JM. Biochemical Pharmacology. 2008 Mar 1; . „Mood disorders: regulation by metabotropic glutamate receptors”. 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. Molecular Psychiatry. 2007 Aug; . „Group-II metabotropic glutamate receptor ligands as adjunctive drugs in the treatment of depression: a new strategy to shorten the latency of antidepressant medication?”. 12 (8): 704—6. PMID 17653204. 
  7. ^ Gewirtz JC, Marek GJ. Neuropsychopharmacology. 2000 Nov; . „Behavioral evidence for interactions between a hallucinogenic drug and group II metabotropic glutamate receptors”. 23 (5): 569—76. PMID 11027922. 
  8. ^ Benneyworth MA, Xiang Z, Smith RL, Garcia EE, Conn PJ, Sanders-Bush E. Molecular Pharmacology. 2007 Aug; . „A selective positive allosteric modulator of metabotropic glutamate receptor subtype 2 blocks a hallucinogenic drug model of psychosis.”. 72 (2): 477—84. PMID 17526600. 
  9. ^ Fischer BD, Miller LL, Henry FE, Picker MJ, Dykstra LA. Psychopharmacology (Berlin). 2008 Apr 8; „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)”. PMID 18392754. 
  10. ^ Fischer BD, Zimmerman EI, Picker MJ, Dykstra LA. Journal of Pharmacology and Experimental Therapeutics. 2008 Feb; . „Morphine in combination with metabotropic glutamate receptor antagonists on schedule-controlled responding and thermal nociception.”. 324 (2): 732—9. PMID 17982001. 
  11. ^ O'Neill MF, Heron-Maxwell C, Conway MW, Monn JA, Ornstein P (2003). „Group II metabotropic glutamate receptor antagonists LY341495 and LY366457 increase locomotor activity in mice”. Neuropharmacology. 45 (5): 565—74. PMID 12941370. doi:10.1016/S0028-3908(03)00232-6. 
  12. ^ Chi H, Jang JK, Kim JH, Vezina P (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. PMID 16901517. doi:10.1016/j.neuropharm.2006.06.008. 
  13. ^ Yoon HS, Jang JK, Kim JH (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. PMID 18675831. doi:10.1016/j.neuropharm.2008.07.012. 
  14. ^ Sakagami K; Yasuhara A; Chaki S; et al. (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”. Bioorg. Med. Chem. 16 (8): 4359—66. PMID 18348906. doi:10.1016/j.bmc.2008.02.066. 

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