| Identification | Back Directory | [Name]
Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-3-[[(3,4-difluorophenyl)thio]methyl]-4-hydroxy-, 2,6-bis[[[(1-methylethoxy)carbonyl]oxy]methyl] ester, (1S,2R,3S,4S,5R,6R)- | [CAS]
1377615-76-3 | [Synonyms]
LY3027788
Bicyclo[3.1.0]hexane-2,6-dicarboxylic acid, 2-amino-3-[[(3,4-difluorophenyl)thio]methyl]-4-hydroxy-, 2,6-bis[[[(1-methylethoxy)carbonyl]oxy]methyl] ester, (1S,2R,3S,4S,5R,6R)- | [Molecular Formula]
C25H31F2NO11S | [MOL File]
1377615-76-3.mol | [Molecular Weight]
591.58 |
| Hazard Information | Back Directory | [Uses]
LY3027788, a diester analog of LY3020371 which is an mGlu2/3 receptor antagonist, is a potent and orally active prodrug of LY3020371. LY3027788 has antidepressant efficacy[1][2]. | [in vivo]
LY3027788 (4.8-27 mg/kg; a single p.o.) produces antidepressant-like decreases in immobility times in the forced-swim test in mice[1].
LY3027788 (4.8-16 mg/kg; a single p.o.) enhances the locomotor stimulant effects of quinpirole at the dose of 16 mg/kg in the locomotor activity assay in mice[1].
LY3027788 (10-30 mg/kg; a single p.o.) dose dependently increases the wake time of rats without engendering rebound hypersomnolence[1].
LY3027788 (a single p.o.) leads to the rapid and dose-proportionate appearance of the pharmacologically active species LY3020371 in plasma of both mouse (4.8-27 mg/kg) and rat (3-30 mg/kg)[1]. | Animal Model: | Male Sprague-Dawley mice (20-25 g)[1] | | Dosage: | 4.8, 16, 27 mg/kg | | Administration: | A single p.o. (60 minutes prior to testing) | | Result: | Potent and efficacious with a minimal effective dose of 16 mg/kg in the mouse forced-swim assay.
The ED60 was 8.2 mg/kg.
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| [IC 50]
mGluR2; mGluR3 | [References]
[1] Witkin JM, et, al. Comparative Effects of LY3020371, a Potent and Selective Metabotropic Glutamate (mGlu) 2/3 Receptor Antagonist, and Ketamine, a Noncompetitive N-Methyl-d-Aspartate Receptor Antagonist in Rodents: Evidence Supporting the Use of mGlu2/3 Antagonists, for the Treatment of Depression. J Pharmacol Exp Ther. 2017 Apr;361(1):68-86. DOI:10.1124/jpet.116.238121
[2] Witkin JM, et, al. mGlu2/3 receptor antagonism: A mechanism to induce rapid antidepressant effects without ketamine-associated side-effects. Pharmacol Biochem Behav. 2020 Mar;190:172854. DOI:10.1016/j.pbb.2020.172854 |
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