کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4346202 1296776 2010 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
LP-211 is a brain penetrant selective agonist for the serotonin 5-HT7 receptor
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
LP-211 is a brain penetrant selective agonist for the serotonin 5-HT7 receptor
چکیده انگلیسی

We have determined the pharmacological profile of the new serotonin 5-HT7 receptor agonist N-(4-cyanophenylmethyl)-4-(2-diphenyl)-1-piperazinehexanamide (LP-211). Radioligand binding assays were performed on a panel of 5-HT receptor subtypes. The compound was also evaluated in vivo by examining its effect on body temperature regulation in mice lacking the 5-HT7 receptor (5-HT7−/−) and their 5-HT7+/+ sibling controls. Disposition studies were performed in mice of both genotypes. It was found that LP-211 was brain penetrant and underwent metabolic degradation to 1-(2-diphenyl)piperazine (RA-7). In vitro binding assays revealed that RA-7 possessed higher 5-HT7 receptor affinity than LP-211 and a better selectivity profile over a panel of 5-HT receptor subtypes. In vivo it was demonstrated that LP-211, and to a lesser degree RA-7, induced hypothermia in 5-HT7+/+ but not in 5-HT7−/− mice. Our results suggest that LP-211 can be used as a 5-HT7 receptor agonist in vivo.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 481, Issue 1, 30 August 2010, Pages 12–16
نویسندگان
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