The effect of three different stereoisomer pairs of CNS (central nervous system) active compounds was sudied on the activity of human mdr1 p-glycoprotein. The methotrimeprazine, clopenthixol and butaclamol isomers had an antiproliferative effect (ID50) on the mdr1 expressing cells at 0.250 μg/ml, while the parental cells were less sensitive having ID50 at 0.37-0.69 μg/ml. Enantiomers of methotrimeprazine and clopenthixol had similar effectivity on the drug efflux of mdr cells. However (-)butaclamol was found to inhibit mdr efflux-pump activity much more than the CNS active (+) isomer. Based on these results, tricyclic compounds does not seem to have stereoselectivity in methotrimeprazine and clopenthixol on the mdr reversal effect. In general, both active and inactive members of stereoisomers had a similar effect on the drug accumulation of the mdr cells. Therefore, hypothetically the CNS inactive member of stereoisomer pairs can be used as a resistance modifier without any risk in patients suffering from drug resistant cancer.
|Number of pages||6|
|Issue number||4 C|
|Publication status||Published - júl. 1 1998|
ASJC Scopus subject areas
- Cancer Research