Poindessous-Jazat F, Schmidt B H, Bassant M H
INSERM U 161, Paris, France.
Eur J Pharmacol. 1998 Dec 11;363(1):17-28. doi: 10.1016/s0014-2999(98)00782-1.
The effects of subchronic administration of metrifonate, a long-lasting cholinesterase inhibitor, on local cerebral glucose utilization were assessed in 3- and 27-month old Sprague-Dawley rats, using the autoradiographic [14C]2-deoxyglucose technique. Rats were treated twice daily with metrifonate (80 or 120 mg/kg) for 3 weeks. The [14C]2-deoxyglucose experiment was performed 18 h after the last metrifonate administration. In 3-month old rats, metrifonate 80 mg/kg increased the average hemispheric cerebral glucose utilization by 12% (P > 0.001). Significant effects were observed in 19 of the 54 regions studied, including cortical and limbic regions. The higher dose induced a larger effect (average increase 17%, 24 of the 54 regions affected). In 27-month old rats, very similar effects were obtained. These results show that repeated administration of metrifonate leads to a sustained metabolic activation in rat brain, at a level comparable to the activation observed previously after a single administration of the drug.
使用放射自显影[14C]2-脱氧葡萄糖技术，评估了长效胆碱酯酶抑制剂敌百虫亚慢性给药对3月龄和27月龄斯普拉格-道利大鼠局部脑葡萄糖利用的影响。大鼠每天接受两次敌百虫（80或120mg/kg）治疗，持续3周。在最后一次给予敌百虫18小时后进行[14C]2-脱氧葡萄糖实验。在3月龄大鼠中，80mg/kg敌百虫使平均半球脑葡萄糖利用率提高了12%（P>0.001）。在所研究的54个区域中的19个区域观察到显著影响，包括皮质和边缘区域。较高剂量诱导的效应更大（平均增加17%，54个区域中的24个受到影响）。在27月龄大鼠中，获得了非常相似的结果。这些结果表明，重复给予敌百虫会导致大鼠脑持续的代谢激活，其水平与先前单次给药后观察到的激活水平相当。
