Inhibition of cellular atp-hydrolyzing activity by tricyclic antidepressants and phenothiazine tranquilizers.

In a variety of cellular and subcellular preparations, total ATP-hydrolyzing activity was potently inhibited by tricyclic antidepressants (TA) and phenothiazine tranquilizers (PT) . In leukocytes, prein~ubation of the cells with 5 x 10 M TA and 1 x 10M PT resulted in up to 878 and 948 inhibition of the ATPase activity . Among TA, dibenzocycloheptadienes were somewhat more potent inhibitors than were derivatives of dibenaazepine . Substitution, at the position 2 of the phenothiazine nucleus, by a halogen and particularly by the CF3 group, increased the inhibitory strength of PT . However, most effective in inhibiting ATPase was thioridazine, structurally differing from mesoridazine, the weakest inhibitor in this study, by a methylmercapto group instead of a methylsulfinyl substituent . The inhibition by the drugs was markedly reduced in the presence of millimolar ATP . The results indicate a possible adverse effect of these drugs on the cellular energy-yielding capacity .