Crean Rebecca D, Davis Sophia A, Taffe Michael A
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA.
Pharmacol Biochem Behav. 2007 May;87(1):11-9. doi: 10.1016/j.pbb.2007.03.015. Epub 2007 Apr 3.
Emergency Department visits and fatalities in which (+/-)3,4-methylenedioxymethamphetamine (MDMA) or (+)methamphetamine (METH) are involved frequently feature unregulated hyperthermia. MDMA and METH significantly elevate body temperature in multiple laboratory species and, most importantly, can also produce unregulated and threatening hyperthermia in nonhuman primates. A majority of prior animal studies have administered drugs by injection whereas human consumption of "Ecstasy" is typically oral, an important difference in route of administration which may complicate the translation of animal data to the human condition.
To determine if MDMA and METH produce hyperthermia in monkeys following oral administration as they do when administered intramuscularly.
Adult male rhesus monkeys were challenged intramuscularly (i.m.) and per os (p.o.) with 1.78 or 5 mg/kg (+/-)MDMA and with 0.1 or 0.32 mg/kg (+)METH. Temperature and activity were monitored with a radiotelemetry system.
Oral administration of either MDMA or METH produced significant increases in body temperature. Locomotor activity was suppressed by MDMA and increased by METH following either route of administration.
The data show that the oral route of administration is not likely to qualitatively reduce the temperature increase associated with MDMA or METH although oral administration did slow the rate of temperature increase. It is further established that MDMA reduces activity in monkeys even after relatively high doses and oral administration.
涉及(±)3,4 - 亚甲基二氧甲基苯丙胺(摇头丸)或(+)甲基苯丙胺(冰毒)的急诊科就诊和死亡事件中,经常出现体温失控性升高。摇头丸和冰毒在多种实验动物中会显著升高体温,最重要的是,它们还会在非人类灵长类动物中引发失控且危险的体温升高。先前的大多数动物研究通过注射给药,而人类服用“摇头丸”通常是口服,给药途径的这一重要差异可能会使动物数据向人类情况的转化变得复杂。
确定摇头丸和冰毒口服给药时是否会像肌肉注射时一样在猴子身上引起体温升高。
成年雄性恒河猴分别通过肌肉注射(i.m.)和口服(p.o.)给予1.78或5 mg/kg的(±)摇头丸以及0.1或0.32 mg/kg的(+)冰毒。使用无线电遥测系统监测体温和活动情况。
口服摇头丸或冰毒均会使体温显著升高。两种给药途径下,摇头丸都会抑制运动活动,而冰毒会增加运动活动。
数据表明,口服给药不太可能从质的方面降低与摇头丸或冰毒相关的体温升高,尽管口服给药确实减缓了体温升高的速度。进一步确定的是,即使在相对高剂量且口服给药后,摇头丸仍会降低猴子的活动。