Non-specific neuroleptic isomer effect on calmodulin-stimulated calcium transport in erythrocyte membrane

Calmodulin-stimulated calcium transport by everted erythrocyte membrane vesicles was inhibited by equivalent doses of active and inactive isomers of the neuroleptic drugs butaclamol and chlorprothixene. However, the trans-isomer of flupenthixol, which lacks neuroleptic properties, inhibited calcium transport more than did the active cis-isomer. The drug concentrations required for inhibition greatly exceeded those serum levels necessary for neuroleptic activity. These results are consistent with a non-specific inhibition of calmodulin-activation of calcium transport by neuroleptic drugs and provide further evidence that this effect is unrelated to clinical antipsychotic properties of these drugs. Effects on basal calcium transport activity indicate binding of neuroleptics at a site other than cytosolic calmodulin.