کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9012881 | 1125025 | 2005 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Use of LC/MS to assess brain tracer distribution in preclinical, in vivo receptor occupancy studies: Dopamine D2, serotonin 2A and NK-1 receptors as examples
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کلمات کلیدی
NK-15-HT2ARacloprideGR205171Receptor occupancy - اشباع گیرندهOlanzapine - الانزاپینIn vivo binding - در in vivo اتصالDopamine - دوپامینSerotonin - سروتونینMass spectroscopy - طیف سنجی جرمیRat - موش صحراییneurokinin - نورو کینینHaloperidol - هالوپریدولliquid chromatography - کروماتوگرافی مایعclozapine - کلوزاپین Gerbil - گربیل
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
کاردیولوژی و پزشکی قلب و عروق
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چکیده انگلیسی
High performance liquid chromatography combined with either single quad or triple quad mass spectral detectors (LC/MS) was used to measure the brain distribution of receptor occupancy tracers targeting dopamine D2, serotonin 5-HT2A and neurokinin NK-1 receptors using the ligands raclopride, MDL-100907 and GR205171, respectively. All three non-radiolabeled tracer molecules were easily detectable in discrete rat brain areas after intravenous doses of 3, 3 and 30 μg/kg, respectively. These levels showed a differential brain distribution caused by differences in receptor density, as demonstrated by the observation that pretreatment with compounds that occupy these receptors reduced this differential distribution in a dose-dependent manner. Intravenous, subcutaneous and oral dose-occupancy curves were generated for haloperidol at the dopamine D2 receptor as were oral curves for the antipsychotic drugs olanzapine and clozapine. In vivo dose-occupancy curves were also generated for orally administered clozapine, olanzapine and haloperidol at the cortical 5-HT2A binding site. In vivo occupancy at the striatal neurokinin NK-1 binding site by various doses of orally administered MK-869 was also measured. Our results demonstrate the utility of LC/MS to quantify tracer distribution in preclinical brain receptor occupancy studies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Life Sciences - Volume 78, Issue 4, 12 December 2005, Pages 340-346
Journal: Life Sciences - Volume 78, Issue 4, 12 December 2005, Pages 340-346
نویسندگان
Eyassu Chernet, Laura J. Martin, Dominic Li, Anne B. Need, Vanessa N. Barth, Karen S. Rash, Lee A. Phebus,