Why dopamine replacement therapy will stay as a cornerstone in the treatment of Parkinson disease: a personal opinion.

In 1961 the use of levodopa was introduced into the treatment of Parkinson's disease (PD). Since bradykinesia seems to reflect the death of dopaminergic nigrostriatal neurons, this observation makes sense. To date, levodopa in combination with a decarboxylase inhibitor is the safest and most efficacious oral treatment in PD. Over the last decades, motor fluctuations, the most important roblem associated with levodopa and due to its short plasma half life have been improved by the addition of MAOB-, COMT-inhibitors and dopamine agonists. Long-acting levodopa formulations are available to keep wearing-off low and to allow the use of 2-3 levodopa tablets per day. Rescue medication, such as oral soluble levodopa/carbidopa or sublingual apomorphine is available as is subcutaneously applied levodopa/carbidopa, a new tool in advice-guided therapy to come near to physiological continuous dopamine receptor stimulation and in this way allow persistent motor control. Most subtances used in PD treatment function via the dopaminergic system. One exception is amantadine, which shows anti-glutamatergic function. At present, modern treatment of PD is a dopamine replacement therapy and probably this will stay that way for a long time to come.