Local anesthetics, mepacrine, and propranolol are antagonists of calmodulin.

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Abstract
Local anesthetics such as dibucaine, QX572 [N,N-bis(phenylcarbamoylmethyl)dimethylammonium chloride], tetracaine and phenacaine and other drugs with local anesthetic-like properties (e.g., mepacrine, propranolol and SKF 525A (.beta.-diethylaminoethyl-2,2-diphenylpentanoate) inhibit the specific calmodulin-dependent stimulation of human erythrocyte Ca2+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) and cyclic nucleotide phosphodiesterases (3'',5''-cyclic-nucleotide 5''-nucleotidohydrolase, EC 3.1.4.17) from brain and heart. Basal activities of these enzymes in the absence of calmodulin are relatively unaffected by concentrations of local anesthetics that strongly inhibit the specific stimulation by calmodulin. Increasing calmodulin, but not Ca2+, overcomes the inhibitory action of the local anesthetics on brain phosphodiesterase. Excess calmodulin does not fully restore activity of erythrocyte Ca2+-stimulated ATPase. Although the mechanism by which the local anesthetics act is unclear, they inhibit binding of 125I-labeled calmodulin to the erythrocyte membrane. Antagonism of calmodulin provides a molecular mechanism that may explain the inhibition of many Ca2+-dependent cellular processes by local anesthetics, e.g., Ca2+ transport, exocytosis, excitation-contraction coupling, non-muscle-cell motility and aggregation.

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