Characteristics of the cytotoxic effects of the phenothiazine class of XXXX antagonists.

@entity1 @entity11922 @entity19 @entity6814 @entity6105 @entity71451 @entity2644 @entity2975 @entity1768 @entity460 @entity25873 @entity5157
We have characterized the antiproliferative effects of the @entity11922 , a group of antipsychotic drugs possessing a wide range of pharmacological actions. The @entity11922 inhibited both the proliferation and clonogenicity of L1210 leukemic lymphocytes. This effect was dependent on both time of exposure and concentration of drug. Clonogenicity of cells in the logarithmic phase of growth was inhibited by greater than 99% at a concentration of drug that had no effect on cells in the plateau phase of growth. @entity1 and @entity19 cell lines, grown either in suspension or in monolayers, were equally susceptible. @entity25873 ( @entity25873 ), purified from L1210 cells by preparative @entity2975 gel electrophoresis, had sensitivity to inhibition by @entity11922 similar to that reported for @entity25873 prepared from brain. The order of potency was @entity6105 greater than or equal to @entity1768 greater than @entity2644 greater than @entity2644 - @entity6814 . As a class, these drugs were less potent antagonists of @entity25873 than was the @entity5157 venom polypeptide, @entity71451 . The antiproliferative effects of @entity11922 were similar to the anticalmodulin effects. Thus, the same order of potencies was seen for both effects; the shapes of the dose-response curves were similarly steep and the effects of excess @entity460 on the inhibition of both were identical. These studies add pharmacological support for @entity25873 being a potential intracellular target for the antiproliferative effect of the @entity11922 .
