کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10964247 | 1102708 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Treatment of rats with an anti-(+)-methamphetamine monoclonal antibody shortens the duration of action of repeated (+)-methamphetamine challenges over a one month period
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کلمات کلیدی
mAb(+)-methamphetamineAMPs.c.i.v.(+)-Amphetamine - (+) - آمفتامینLC–MS/MS - LC-MS / MSt1/2 - t1 / 2Monoclonal antibody - آنتی بادی مونوکلونالIntravenous - داخل وریدیsubcutaneous - زیر جلدیDrug abuse - سوء مصرف موادMETH - متهMethamphetamine - متیل آمفتامینChronic administration - مدیریت مزمنPreclinical studies - مطالعات پیش از موعدRats - موش صحراییterminal elimination half-life - نیمه عمر حذف ترمینالliquid chromatography coupled to tandem mass spectrometry - کروماتوگرافی مایع همراه با طیف سنجی جرمی دو طرفه
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
This study assessed clinical scenarios of continuing monoclonal antibody (mAb) treatment for (+)-methamphetamine (METH) addiction, and the implications of missing or discontinuing this therapy. We hypothesized that chronic anti-METH mAb7F9 (METH KD = 9 nM) treatment of rats could significantly decrease METH-induced behaviors; even with repeated METH challenges, use of METH doses in excess of mAb binding sites, and after discontinuing mAb treatment which results in a 10-fold reduction in mAb7F9 serum concentrations. Male Sprague Dawley rats (n = 6/group) were treated with i.v. saline or a loading dose of mAb7F9 to achieve instant steady-state conditions followed by two weekly (141 mg/kg) doses ending on day 14. METH (0.56 mg/kg) was administered 4 h and three days after each saline or mAb7F9 treatment, and on day 21. This produced locomotion and rearing behavior that lasted about 120 min in control rats. In mAb7F9 treated rats, METH-induced distance traveled was significantly reduced from 60 to 120 min (P < 0.05) on days 0-21 and rearing was significantly reduced from 60 to 120 min on days 0-17. METH serum concentrations determined 5 h after METH dosing was significantly increased in mAb7F9-treated rats after all METH challenges. On days 24 and 28 (the final day), the rats were administered a 3-fold higher METH dose (1.68 mg/kg). MAb7F9 treated rats showed a substantially earlier termination of the METH-induced locomotion on both days, even though the METH dose exceeded mAb7F9s binding capacity. METH brain concentrations determined 5 h after METH on day 28 were also significantly decreased in mAb7F9-treated rats. In conclusion, over one month, mAb7F9 significantly and continuously bound METH and reduced METH-induced locomotor effects even after discontinuation of mAb treatment and challenge with higher METH doses.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vaccine - Volume 32, Issue 47, 29 October 2014, Pages 6213-6219
Journal: Vaccine - Volume 32, Issue 47, 29 October 2014, Pages 6213-6219
نویسندگان
Michael D. Hambuchen, Daniela Rüedi-Bettschen, D. Keith Williams, Howard Hendrickson, S. Michael Owens,