New dopamine agonists for the treatment of Parkinson's disease

The development of motor fluctuations and dyskinesias remains a challenge in the treatment of advanced Parkinson's disease. These complications are associated with the dosage and duration of levodopa therapy, therefore a long-term levodopa monotherapy should be avoided. The early introduction of dopamine agonists and concomitant reduction of levodopa is considered to delay the occurrence of levodopa-associated complications and to improve already existing fluctuations. In addition to the established oral ergoline dopamine agonists bromocriptine, lisuride and pergolide new compounds have been developed and investigated in studies to further improve long-term therapy of Parkinson's disease. Dihydroergocriptine and cabergoline are also ergoline dopamine agonists. These drugs differ mainly with regard to pharmacokinetic properties (long plasma half-life) and affinity for dopamine D1 receptors. Ropinirole and pramipexole are two non-ergoline derivates without affinity for D1 receptors but with high affinity for the dopamine D3 receptor subtype. Since comparative studies for most compounds are lacking, dopamine agonists should be selected according to individual efficacy and tolerability and cost effectiveness in the individual patient.