Malekzadeh Pouran, Hu Jackie, Sandweiss Alexander J, Ameli Nina, Bierny Philippe, Largent-Milnes Tally M, Vanderah Todd W, Shirazi Farshad
College of Medicine, University of Arizona, Tucson, AZ, USA.
Department of Pharmacology, University of Arizona, Tucson, AZ, USA.
J Pharm Pharmacol (Los Angel). 2017 Apr;5(1). doi: 10.13188/2327-204X.1000020. Epub 2017 Apr 20.
Methamphetamine (MA) toxicity is a major health concern causing agitation, hyperkinesia, hyperthermia, and even death, affecting 24.7 million people worldwide. It has been observed that MA generates movement disorders in children similar to that of scorpion envenomation. Four cases have been reported where MA intoxication in children were both subjectively and objectively improved as indicated by the reversal of nystagmus and movement disorders following administration of Centruroides antivenom (AV) therapy.
Here, we aimed to demonstrate the reversal of MA induced movement disorders and hyperthermia by scorpion AV equine immune F(ab')2 in rats.
Baseline core temperature and locomotor activity in adult male Sprague-Dawley rats (200-220 g) were evaluated prior to acute administration of AV (20 mg/kg, intraperitoneally, i.p.) + MA (10 mg/kg, i.p.) or control. Core body temperature was reassessed 10, 50, and 80 min post injection while locomotor activity was reassessed 20-35 and 60-75 min post injection.
At 20-35 min, Saline + MA and BSA + MA groups showed a significant increase in the number of fine events compared to their respective control groups Saline + Saline and BSA + Saline, which indicates an increase in paw movements of animals ( = 0.008, = 0.006, respectively). In contrast, AV + MA demonstrated a non-significant increase in fine activity compared to the control group AV + Saline). At 60-75 min, the AV + MA treatment group were less likely to engage in locomotor activity indicated by the significant decrease in exploratory events compared to BSA + MA control group ( = 0.041). No significant percent change in core body temperature was observed in the AV + MA treatment group compared to the control groups, AV + Saline and BSA + MA.
Here, we provide evidence for some aspects of MA-induced hyperkinesia but not hyperthermia reversed by scorpion AV. Further preclinical studies involving adolescent rodents may be necessary to completely mimic the reversal of MA toxicity seen in children in the clinic.
甲基苯丙胺（MA）中毒是一个主要的健康问题，可导致激动、运动亢进、体温过高甚至死亡，影响着全球2470万人。据观察，MA在儿童中引发的运动障碍与蝎子蜇伤类似。已有4例报道称，给予Centruroides抗蛇毒血清（AV）治疗后，儿童MA中毒的主观和客观症状均得到改善，如眼球震颤和运动障碍的逆转。
在此，我们旨在证明蝎子AV马免疫F(ab')2可逆转大鼠中MA诱导的运动障碍和体温过高。
在急性给予AV（20mg/kg，腹腔注射，i.p.）+MA（10mg/kg，i.p.）或对照组之前，评估成年雄性Sprague-Dawley大鼠（200-220g）的基线核心体温和运动活动。注射后10、50和80分钟重新评估核心体温，注射后20-35和60-75分钟重新评估运动活动。
在20-35分钟时，生理盐水+MA组和牛血清白蛋白+MA组与各自的对照组生理盐水+生理盐水组和牛血清白蛋白+生理盐水组相比，细微活动次数显著增加，这表明动物的爪部运动增加（分别为P=0.008，P=0.006）。相比之下，AV+MA组与对照组AV+生理盐水组相比，细微活动增加不显著。在60-75分钟时，与牛血清白蛋白+MA对照组相比，AV+MA治疗组进行运动活动的可能性较小，探索活动显著减少（P=0.041）。与对照组AV+生理盐水组和牛血清白蛋白+MA组相比，AV+MA治疗组的核心体温没有观察到显著的百分比变化。
在此，我们提供了证据表明蝎子AV可逆转MA诱导的运动亢进的某些方面，但不能逆转体温过高。可能需要进一步涉及青春期啮齿动物的临床前研究，以完全模拟临床上在儿童中看到的MA毒性的逆转情况。
