Correlation between brain/plasma ratios and efficacy in neuropathic pain models of selective metabotropic glutamate receptor 1 antagonists

…, T Kolasa, M Patel, OF El Kouhen, R Chang…

文献索引：Zheng, Guo Zhu; Bhatia, Pramila; Kolasa, Teodozyj; Patel, Meena; El Kouhen, Odile F.; Chang, Renjie; Uchic, Marie E.; Miller, Loan; Baker, Scott; Lehto, Sonya G.; Honore, Prisca; Wetter, Jill M.; Marsh, Kennan C.; Moreland, Robert B.; Brioni, Jorge D.; Stewart, Andrew O. Bioorganic and Medicinal Chemistry Letters, 2006 , vol. 16, # 18 p. 4936 - 4940

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被引用次数: 25

摘要

We have discovered a novel, potent, and selective triazafluorenone series of metabotropic glutamate receptor 1 (mGluR1) antagonists with efficacy in various rat pain models. Pharmacokinetic and pharmacodynamic profiles of these triazafluorenone analogs revealed that brain/plasma ratios of these mGluR1 antagonists were important to achieve efficacy in neuropathic pain models. This correlation could be used to guide our in vivo SAR ( ...