Frisch W, Lüllmann-Rauch R
Acta Neuropathol. 1980;52(3):179-87. doi: 10.1007/BF00705806.
The present study is concerned with the question of whether or not amphiphilic drugs (chloroquine, quinacrine, perhexiline) that fail to induce general lipidosis in the central nervous system (CNS) of adult rats can produce lipidosis in a circumventricular organ (area postrema) not furnished with a blood-brain barrier. Chlorphentermine known to induce general lipidosis in CNS of adult rats served as reference compound. All drugs, when chronically applied in high oral doses, induced significant perikaryal lipidosis in the area postrema. In the adjacent nuclei (nucleus tractus solitarii, nucleus dorsalis nervi vagi, nucleus nervi hypoglossi, nucleus gracilis), only chlorphentermine caused generalized lipidosis, whereas the other drugs had either limited or no effects. The present findings strongly suggest that the exemption, of most regions of the CNS of adult rats, from lipidosis induced by chloroquine and others is due to hindered drug distribution across the blood-brain barrier, rather than being due to non-susceptibility of central neurons toward the lipidosis-inducing action of the drugs.
本研究关注的问题是,未能在成年大鼠中枢神经系统(CNS)中诱发全身性脂质沉积症的两亲性药物(氯喹、喹吖因、哌克昔林)是否能在没有血脑屏障的室周器官(最后区)产生脂质沉积症。已知能在成年大鼠中枢神经系统诱发全身性脂质沉积症的氯苯丁胺用作参考化合物。所有药物长期大剂量口服给药时,均在最后区诱发了明显的核周脂质沉积症。在相邻核团(孤束核、迷走神经背核、舌下神经核、薄束核)中,只有氯苯丁胺引起了全身性脂质沉积症,而其他药物要么作用有限,要么没有作用。目前的研究结果有力地表明,成年大鼠中枢神经系统的大多数区域对氯喹等药物诱发的脂质沉积症具有抵抗力,是由于药物在血脑屏障中的分布受阻,而不是由于中枢神经元对药物诱导脂质沉积症的作用不敏感。