Tamoxifen is a calmodulin antagonist in the activation of cAMP phosphodiesterase.

The mechanism of action of tamoxifen, a triphenylethylene antiestrogen with antitumor activity, has not been fully established. In this paper, we present evidence that tamoxifen is an antagonist of calmodulin, a major cellular calcium receptor and calcium dependent regulator of many cellular processes. Our data showed that tamoxifen inhibited the activation of phosphodiesterase by calmodulin. This inhibition could be overcome by an increase in calmodulin concentration. Kinetic analysis demonstrated that tamoxifen is a competitive inhibitor of calmodulin in the activation of this enzyme. It could be speculated that the antagonism of calmodulin by tamoxifen may be one of the mechanisms responsible for its pharmacological actions.