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.