Inhibition of monoamine synthesis by irreversible blockade of aromatic aminoacid decarboxylase with alpha-monofluoromethyldopa.

DL-α-monofluoromethyldopa is a potent enzyme-activated irreversible inhibitor of purified aromatic aminoacid decarboxylase. Single doses from 0.25 to 25 mg/kg cause partial to total inhibition of this enzyme in kidney and heart. Inhibition of brain enzyme becomes significant at doses above 2.5 mg/kg and is complete at 100 mg/kg. Enzyme activity begins to return after 24 hr, so that repetition of a dose at 12 hr intervals markedly increases the inhibition. Single doses of 100–250 mg/kg almost completely deplete kidney, heart and brain of endogenous catecholamines by blocking dopa decarboxylation. Serotonin is also decreased, presumbaly by the same mechanism.