2. Pharmacologic effects—Levodopa

2. Pharmacologic effects—Levodopa ameliorates the signs of parkinsonism, particularly bradykinesia; moreover, the mortality rate is decreased. However, the drug does not cure parkinsonism, and responsiveness fluctuates and gradually decreases with time, which may reflect progression of the disease. Clinical response fluctuations may, in some cases, be related to the timing of levodopa dosing. In other cases, unrelated to dosing, off-periods of akinesia may alternate over a few hours with on-periods of improved mobility but often with dyskinesias (on-off phenomena). In some case, off-periods may respond to apomorphine. Although drug holidays sometimes reduce toxic effects, they rarely affect response fluctuations. However, catechol-O-methyltransferase (COMT) inhibitors used adjunctively may improve fluctuations in levodopa responses in some patients