کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9921444 | 1559221 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Disconnection between the early onset anorectic effects by C75 and hypothalamic fatty acid synthase inhibition in rodents
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
In order to explore the relationship between the anorectic effect of 3-carboxy-4-octyl-2-methylenebutyrolactone (C75) and its pharmacokinetic properties, studies of in vivo and in vitro pharmacological characterization of C75 were performed in Fischer rats. In a quantitative measurement of food intake, we determined that appetite suppression by C75 takes place within 4 h. The Cmax for C75 of 2.6±1.5 μM was reached within 1-4 h after intraperitoneal administration at 30 mg/kg, a drug level that causes complete blockade of food intake. However, this concentration is substantially lower than the effective concentration used to inhibit rat fatty acid synthase enzyme activity in vitro (IC50: â¼200 μM) and hypothalamic enzyme activity was found not to be inhibited by intraperitoneal administration of C75 at 30 mg/kg. Instead, a dramatic induction of c-Fos expression was found in area postrema. Collectively, these data indicate that the anorectic effect of C75 is independent of its inhibition of fatty acid synthase in the hypothalamus.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 511, Issue 1, 21 March 2005, Pages 31-41
Journal: European Journal of Pharmacology - Volume 511, Issue 1, 21 March 2005, Pages 31-41
نویسندگان
Kenneth W. Rohrbach, Songping Han, Jinping Gan, Eva J. O'Tanyi, Hongwei Zhang, Cecilia L. Chi, Rebecca Taub, Brian L. Largent, Dong Cheng,