Study M116
Study name | Witkin JM 2017 |
Title | 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 |
Overall design | The aim of this study was to compare in vivo biological responses in rodents elicited by a recently discovered mGlu2/3 receptor antagonist (LY3020371) with those produced by ketamine. The metabolomic profiles from rat CSF and hippocampus of ketamine and LY3020371 were compared. Rats were divided into 3 groups: (1) control group, (2) LY group (LY3020371 treatment at single dose of 10 mg/kg i.p.), (3) ketamine group (ketamine treatment at single dose of 10 mg/kg i.p.). Tissue from hippocampus and cerebrospinal fluid (CSF) were harvested at 1 hour postdosing. Analytes displayed significant differentiation from those detected in vehicle-treated animals in both CSF and hippocampus were identified using hydrophilic-interaction chromatography-liquid chromatography mass spectrometer discovery platform. |
Study Type | Type3; |
Data available | Unavailable |
Organism | Rat; Sprague-Dawley rat; |
Categories of depression | Healthy individuals; Healthy individuals; Healthy individuals; |
Criteria for depression | Forced swimming test |
Sample size | N/A |
Tissue | Central; Cerebrospinal fluid; Cerebrospinal fluid; Central; Brain; Hippocampus; |
Platform | MS-based; LC-MS: hydrophilic-interaction chromatography-liquid chromatography mass spectrometer discovery platform; |
PMID | |
DOI | |
Citation | Witkin JM, Mitchell SN, Wafford KA, 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;361(1):68-86. |
Metabolite | Stearic acid; Methylimidazoleacetic acid; Glycine; Succinic acid; D-Glucose; Choline; Dimethylglycine; N1-Methyl-4-pyridone-3-carboxamide; Hydroxylamine; Ascorbic acid; Fumaric acid; Pyruvic acid; Betaine; Trimethylamine N-oxide; Niacinamide; 4-Hydroxyproline; D-Xylitol; D-Ribose; Cyclic AMP; Glycolic acid; Hydroxyisocaproic acid; ADP-glucose; Thiamine monophosphate; Adenosine; 2-Ketohexanoic acid; 1-Methylnicotinamide; Citicoline; Sucrose; Alpha-Tocopherol; Heptadecanoic acid; Shikimic acid; Indoleacrylic acid; 4-Pyridoxic acid; O-Phosphoethanolamine; Proline betaine; Methylcysteine; Erythro-Pentonic acid, 2-deoxy-3,4,5-tris-O-(trimethylsilyl)-, trimethylsilyl ester; Phosphocreatine; L-Norleucine; Erythrose; Mannitol; Formamide; Dephospho-CoA; Pyridoxamine; 4-Hydroxyphenylpyruvic acid; gamma-Glutamylglutamic acid; Amino-methylpyrimidine; Argininic acid; (S)-3,4-Dihydroxybutyric acid; 2-Deoxypentonic acid; Thiamine; Ornitine; N-Formylglycine; 2-Monostearin; L-Sorbose; 2-O-Glycerol-galactopyranoside; Hydroxypropionic acid; 1,5-Anhydrosorbitol; UDP-AcGlcamine; Dimethyl sulfone; |
