Parkinson’s disease-like movement disorders. Therefore, the motor dysfunctions
observed in patients chronically treated with antipsychotics are seemingly due to alter-
ations in D2 receptor density.
4.4.2 Presynaptic Dopaminergic Drug EffectsPresynaptic dopamineregic drug effects may be subdivided in the same way as that in
which adrenergic drugs were classified in section 4.3.5:
- Dopamine synthesis inhibitors
- Dopamine metabolism inhibitors
- Dopamine storage inhibitors
- Dopamine reuptake inhibitors
- Presynaptic dopaminergic agonists
These enable a logical, mechanistic understanding and will be discussed individually.
4.4.2.1 Dopamine Synthesis Inhibitors
Dopamine synthesis inhibitors interfere with the enzymes involved, and are identical to
those discussed in section 4.3.5 (e.g.,α-methyltyrosine (4.74), a tyrosine hydroxylase
inhibitor). In this case,α 2 -adrenergic receptor effects are irrelevant, and only the clas-
sical competitive inhibitory effect is of any consequence.
Carbidopa (4.75), a hydrazine analog of α-methyldopa, is an important DOPA decar-
boxylase inhibitor. It is used to protect the DOPA that is administered in large doses in
Parkinson’s disease (section 4.4.4) from peripheral decarboxylation. DOPA concentra-
tions in the CNS will therefore increase without requiring the administration of
extremely high, toxic doses of DOPA. The exclusive peripheral mode of action of car-
bidopa is due to its ionic character and inability to cross the blood–brain barrier. Because
of this effect, carbidopa is co-administered with DOPA in a single tablet formulation as
a first-line therapy for Parkinson’s disease. Benserazide (4.76) has similar activity.
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