Calmodulin drug interactions

Chloroquine (Aralen) is one of several 4-aminoquino-line derivatives that display antimalarial activity. Chloroquine is particularly effective against intraerythrocytic forms because it is concentrated within the parasitized erythrocyte. This preferential drug accumulation appears to occur as a result of specific uptake mechanisms in the parasite. Chloroquine appears to work by intercalation with DNA, inhibition of heme polymerase or by interaction with Ca++-calmodulin-mediated mechanisms. It also accumulates in the parasite s food vacuoles, where it inhibits peptide formation and phospholipases, leading to parasite death. 

We also have used 19F NMR and ICD spectra to study interactions of trifluoperazine with calmodulin under various conditions where no aggregation of trifluoperazine occurs. Antipsychotic drugs such as trifluoperazine (TFP) are strongly bound to calmodulin (CaM) in the presence of Ca2+ and behave as potent CaM antagonists I60161>. 

Trifluoperazine, 10-[3-(4-methyl-l-piperazinyl)pro-pyl]-2-trifluoromethylthiophenazine, a drug that binds to Ca -calmodulin and inhibits its interaction with other proteins, reversibly inhibited growth and phagocytosis of polyvinyltoluene latex beads (2.97 pm diameter) in a macrophagelike cell line, J774.16 (Horwitz et al. 1981). 

There may be an interaction of the two drugs on the calcineurin-calmodulin-calcium complex, on which both alcohol and tacrolimus/ pimecrolimus are known to act. 

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