Parkinsonism: Levodopa, Carbidopa, and Other Drugs
Treatment
aims to replenish dopamine, or at least to reestablish the
balance between dopamine and ACh influences on striatal neurons. Dopamine
cannot cross the bloodbrain barrier, so its metabolic precursor, levodopa, is
used. Most of an oral dose is rapidly converted to dopamine by dopa
decarboxylase located in blood vessel walls. Approximately 1% to 5% of the dose
crosses the bloodbrain barrier, enters metabolic pathways of dopaminergic
neurons, and is converted to dopamine. To increase the amount
of levodopa that enters the brain, it is usually given with an
inhibitor of dopa decarboxylase (such as carbidopa) that does not easily cross
the bloodbrain barrier. Peripheral conversion of levodopa to dopamine is thus
reduced, so more levodopa enters the brain. Adverse effects include the onoff
effect, arrhythmias, and hypotension. Directacting dopamine receptor agonists,
inhibitors of dopamine metabolism (eg, MAOIs), anticholinergic agents,
and amantadine are other drug options.
