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…
Index: 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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Citation Number: 25
Abstract
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 ( ...
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[Zheng, Guo Zhu; Bhatia, Pramila; Daanen, Jerome; Kolasa, Teodozyj; Patel, Meena; Latshaw, Steven; El Kouhen, Odile F.; Chang, Renjie; Uchic, Marie E.; Miller, Loan; Nakane, Masaki; Lehto, Sonya G.; Honore, Marie P.; Moreland, Robert B.; Brioni, Jorge D.; Stewart, Andrew O. Journal of Medicinal Chemistry, 2005 , vol. 48, # 23 p. 7374 - 7388]
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