کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1376764 981964 2006 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Correlation between brain/plasma ratios and efficacy in neuropathic pain models of selective metabotropic glutamate receptor 1 antagonists
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Correlation between brain/plasma ratios and efficacy in neuropathic pain models of selective metabotropic glutamate receptor 1 antagonists
چکیده انگلیسی

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 (structure–activity relationship) modification. For example, compound 4a has a brain/plasma ratio of 0.34, demonstrating only moderate efficacy in neuropathic pain models. On the other hand, antagonist 4b with a brain/plasma ratio of 2.70 was fully efficacious in neuropathic pain models.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 16, Issue 18, 15 September 2006, Pages 4936–4940
نویسندگان
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