The effects of colchicine in mammalian brain from rodents to rhesus monkeys.
The injection of colchicine into rats and monkeys produced two different types of brain damage. At selected doses, intradentate colchicine preferentially destroyed DGC in rats, whereas damage was less selective and more severe in monkeys. Experiments were performed with different tubulin-binding drugs to investigate the structure-function relationship of tubulin binding and DGC death. The tubulin-binding characteristics of these and other drugs reported in the literature did not correlate with their ability to damage DGC. The role of seizure-induced cell death was investigated by recording the EEG in monkeys and in rats treated with phenobarbital. The data suggest that seizures are an infrequent epiphenomenon of colchicine's action. We proposed that colchicine is not a selective neurotoxin and that it causes brain damage by inducing a non-specific inflammatory response. This response is both dose- and species-dependent. We concluded by discussing the medical implications of the present and proposed uses of colchicine.
Dasheiff
R M
RM
Ramirez
L F
LF
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects; D001812:Blood-Brain Barrier; D001927:Brain Diseases / Q000139:chemically induced; D002415:Cats; D003078:Colchicine / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D006224:Cricetinae; D004285:Dogs; D004569:Electroencephalography; D004660:Encephalitis / Q000139:chemically induced; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D008253:Macaca mulatta; D008297:Male; D051379:Mice; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures / Q000139:chemically induced; D013045:Species Specificity; D014404:Tubulin / Q000378:metabolism; D014747:Vinblastine / Q000494:pharmacology
D014404:Tubulin; D014747:Vinblastine; D003078:Colchicine