Gentry W Brooks, Laurenzana Elizabeth M, Williams D Keith, West Jeremy R, Berg Renata J, Terlea Teodora, Owens S Michael
University of Arkansas for Medical Sciences, Department of Anesthesiology, College of Medicine, Little Rock, AR 72205, United States.
Int Immunopharmacol. 2006 Jun;6(6):968-77. doi: 10.1016/j.intimp.2006.01.008. Epub 2006 Feb 9.
The purpose of these studies was to determine if a high-affinity, anti-(+)-methamphetamine (METH) monoclonal antibody (mAb6H4; KD=11 nM) protects against METH-induced central nervous and cardiovascular system effects in rats. Rats (n=5 per group) received one of three anti-METH mAb6H4 doses, equal to 0.32, 0.56 or 1 times the mole equivalent (mol-eq) amount of METH in the body following a 1 mg/kg i.v. METH dose. Each rat was challenged with METH (1 mg/kg, i.v.) 1 and 4 days after the anti-METH mAb dose. The 1 mol-eq anti-METH mAb dose significantly reduced the duration of METH-induced locomotor activity (horizontal locomotion and rearing events), heart rate and blood pressure effects from 2 to 3 h to about an hour. This resulted in a significant reduction in total locomotor activity and the area under the hemodynamic effect vs. time curve for heart rate and blood pressure. In addition, the time to peak locomotor activity was decreased after the 1 mol-eq mAb dose vs. the lower doses. These changes were limited to the first METH challenge. The responses to the second METH challenge were not different from baseline. The peak hemodynamic and locomotor activity values were unchanged after both challenges. These results indicate anti-METH mAb6H4 can safely reduce the hemodynamic and locomotor effects of METH given one day after anti-METH IgG, and that the mAb is safe when administered in the absence of METH. These results are important because they indicate these antibody medications have simultaneous beneficial effects in multiple organ systems.
这些研究的目的是确定一种高亲和力的抗（+）-甲基苯丙胺（METH）单克隆抗体（mAb6H4；KD = 11 nM）是否能保护大鼠免受METH诱导的中枢神经和心血管系统影响。大鼠（每组n = 5）接受三种抗METH mAb6H4剂量之一，其剂量相当于静脉注射1 mg/kg METH后体内METH摩尔当量（mol-eq）的0.32、0.56或1倍。在抗METH mAb给药后的第1天和第4天，每只大鼠接受METH（1 mg/kg，静脉注射）激发。1 mol-eq抗METH mAb剂量显著缩短了METH诱导的运动活动（水平运动和竖毛事件）、心率和血压影响的持续时间，从2至3小时缩短至约1小时。这导致总运动活动以及心率和血压的血流动力学效应与时间曲线下面积显著降低。此外，与较低剂量相比，1 mol-eq mAb剂量后运动活动达到峰值的时间缩短。这些变化仅限于首次METH激发。对第二次METH激发的反应与基线无差异。两次激发后血流动力学和运动活动的峰值均未改变。这些结果表明，抗METH mAb6H4在抗METH IgG给药一天后能安全降低METH的血流动力学和运动效应，且在无METH时给药该mAb是安全的。这些结果很重要，因为它们表明这些抗体药物在多个器官系统中具有同时的有益作用。
