Fluphenazine-N-2-chloroethane·2HCl

Fluphenazine-N-2-chloroethane is a nitrogen mustard-containing derivative of Fluphenazine dihydrochloride that demonstrates irreversible inhibition of CaM-induced activation of CNPase (cyclic nucleotide phosphodiesterase). Inclusion of the alkylating nitrogen mustard moiety in Fluphenazine-N-2-chloroethane produces irreversible deactivation of CaM, while the parent compound demonstrates a reversible inhibitory activity. CaM antagonism is shown to sensitize malignant cells to TRAIL (tumor necrosis factor related apoptosis-inducing ligand) necrotic signaling, promoting cell death in TRAIL-resistant growth. Fluphenazine-N-2-chloroethane is further shown to irreversibly antagonize dopamine receptors with selectivity for D2DR over D1DR. Inhibition of the dopamine receptors by Fluphenazine-N-2-chloroethane correlated to an increase in D2DR mRNA, a decrease in D1DR mRNA, and an increase in glutamic acid decarboxylase mRNA, indicating that this inhibition of dopamine receptor activity has a regulatory role in the cellular expression of dopaminergic and GABAergic proteins.