The toxicity of thioxanthene neuroleptics to isolated rat liver cells.
A series of thioxanthenes was tested for cytotoxicity to isolated rat hepatocytes, as measured by the loss of an intracellular enzyme (GOT) to the surrounding medium. The relative order of potency was found to be: SKF 10812 greater than cis- = trans-chlorprothixene = N-756A greater than cis- = trans-flupenthixol greater than xanthiol greater than methixene = cis- = trans-clopenthixol = N-716 greater than N-710. The presence of an unsaturated exocyclic bond increased the apparent toxicity as did the presence of a substituent (trifluoromethyl, chlorine, bromine) at the two position of the tricyclic nucleus. The trifluoromethyl substituted thioxanthenes were three to four times more potent than their halogenated analogs, but there were no differences in potency among the halogenated (chlorine or bromine) thioxanthenes. Compounds which had a dimethylaminopropylidene side chain were five to six times stronger in causing enzyme leakage than were their analog which had a hydroxyethylpiperazinylpropylidene side chain. Although only the cis-isomers of each compound are highly active neuroleptics, both isomers were equipotent at causing the efflux of GOT from rat hepatocytes.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D002478:Cells, Cultured; D003470:Culture Media; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051381:Rats; D013892:Thioxanthenes / Q000633:toxicity*
D003470:Culture Media; D013892:Thioxanthenes; D001219:Aspartate Aminotransferases