Effects of several lipidosis-including drugs upon the area postrema and adjacent medullary nuclei of adult rats. I. Alterations is perikarya and dendrites.
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.
D000818:Animals; D001812:Blood-Brain Barrier; D001927:Brain Diseases / Q000139:chemically induced*; D002738:Chloroquine / Q000494:pharmacology*; D002745:Chlorphentermine / Q000494:pharmacology; D005260:Female; D008064:Lipidoses / Q000139:chemically induced*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000648:ultrastructure; D008854:Microscopy, Electron; D010480:Perhexiline / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D013997:Time Factors
D010880:Piperidines; D002738:Chloroquine; D011796:Quinacrine; D010480:Perhexiline; D002745:Chlorphentermine