Effect of Centruroides antivenom on reversal of methamphetamine-induced hyperkinesis and hyperthermia in rats

J Pharm Pharmacol (Los Angel). 2017 Apr;5(1):5. doi: 10.13188/2327-204X.1000020. Epub 2017 Apr 20.


Context: 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.

Objective: Here, we aimed to demonstrate the reversal of MA induced movement disorders and hyperthermia by scorpion AV equine immune F(ab')2 in rats.

Materials and methods: 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.

Results: 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 in situ (p = 0.008, p = 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 (p = 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.

Discussion: 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.

Keywords: Antivenom; antivenins; mechanism; methamphetamine; rats; symptomatology.