Psychotropic drugs and local anesthetics restore cardiolipin-inhibited mammalian DNA topoisomerase I activity.
The activity of mammalian topoisomerase I is inhibited by acidic phospholipids. We investigated the effect of psychotropic drugs and local anesthetics on cardiolipin-inhibited calf thymus DNA topoisomerase I activity. Chlorpromazine, promethazine, and imipramine, which interact with phospholipids, suppressed the inhibitory effect of cardiolipin. The present results suggest that relaxation of DNA supercoiling is involved in the cytotoxic action of these drugs.
Shah
G H
GH
Department of Microbiology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kataoka
K
K
Ueno
A
A
Ohtsuka
Y
Y
Mizushima
T
T
Sekimizu
K
K
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D002308:Cardiolipins / Q000494:pharmacology*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D007202:Indicators and Reagents; D011398:Promethazine / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology*; D013950:Thymus Gland / Q000201:enzymology; D059004:Topoisomerase I Inhibitors
D000779:Anesthetics, Local; D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D002308:Cardiolipins; D006993:Hypnotics and Sedatives; D007202:Indicators and Reagents; D011619:Psychotropic Drugs; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; D011398:Promethazine; D007099:Imipramine; D002746:Chlorpromazine