The arylamino acid decarboxylase inhibitory action of DL-α-fluoromethyldopa
(4.77) has also been described. By affecting the enzyme through covalent binding, this
compound completely inhibits both catecholamine and serotonin synthesis. Unlike
6-hydroxydopamine,α-fluoromethyldopa does not destroy the neurons, and unlike
reserpine it does not deplete chromaffin tissue in the adrenal gland.
4.4.2.2 Dopamine Metabolism Inhibitors
Dopamine metabolism inhibitors interfere with monoamine oxidase and catecholamine-
O-methyltransferase. Monoamine oxidase will be discussed separately in chapter 8.
4.4.2.3 Dopamine Storage Inhibitors
The storage and release of DA can be modified irreversibly by reserpine (3.1), just as
in vesicles containing other catecholamines and serotonin. Dopamine release can be
blocked specifically by γ-hydroxybutyrate (4.78) or its precursor, butyrolactone, which
can cross the blood–brain barrier. High doses of amphetamines do deplete the storage
vesicles, but this is not their principal mode of action. Apparently, amantadine (4.79),
an antiviral drug that is likewise beneficial in parkinsonism (and also perhaps to relieve
fatigue in multiple sclerosis), may also act by releasing DA.
4.4.2.4 Dopamine Reuptake Inhibitors
Dopamine reuptake can be inhibited specifically by benztropine (4.80), an anticholin-
ergic drug, as well as by amphetamines.Several specific DA reuptake inhibitors have
been discovered, such as tandamine (4.81), bupropion (4.82), and nomifensine (4.83),
which are all potent antidepressants. Tandamine also inhibits NE uptake.
NEUROTRANSMITTERS AND THEIR RECEPTORS 241