Calmodulin antagonists chlorpromazine and W‐7 inhibit exogenous cholesterol esterification and sphingomyelinase activity in human skin fibroblast cultures. Similarities between drug‐induced and niemann‐pick type C lipidoses

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Abstract
In this report we showed that calmodulin antagonists chlorpromazine (CPZ) and W-7 (N-[6- aminohexyl]-5-chloro-1-naphtalenesulfonamide), when added to fibroblast cell cultures, gave rise to a time- and dose dependent decrease of sphingomyelinase activity. CPZ and W-7 also significantly inhibited LDL- and non-LDL- dependent cholesterol esterification. Addition of these drugs to cell culture medium mimicked what is observed in the genetic disease Niemann-Pick type C.H-7 (1-[5-isoquinonylsulfonyl]-2-methylpiperazine), an inhibitor of protein kinase C and cyclic nucleotide-dependent kinases, had no effect on sphingomyelinase and cholesterol ester formation. Thus the possibility of a modulation of cell sphingomyelin and cholesterol esters by a calmodulin-dependent second messenger system must be considered.