A comparison of dopamine agonists

Dopamine agonists are an integral and essential component of the current drug treatment of parkinson's disease. While in the past the administration of dopamine agonists was mostly restricted to advanced parkinson's disease where they were combined with levodopa (plus one of the other decarboxylase inhibitor), there is a growing trend today to administer dopamine agonists in early stages and even as monotherapy, i.e. without levodopa. If combined with levodopa dopamine agonists allow for reduced dosages of levodopa. All available dopamine agonists stimulate dopamine D-2 receptors of postsynaptic neurons. They differ, however, in their potency and selectivity for dopamine receptor subtypes. The parallel stimulation by dopamine D-2 agonists of the dopamine autoreceptors of the presynaptic neurons which are also of the D-2 type reduces dopamine turnover. This is suggested to yield neuroprotection. Compared to levodopa dopamine agonist treatment is accompanied by an increased incidence of some adverse events including hallucinations, nausea and vomiting. Moreover, the full effect is not to be expected before 3 - 11 weeks of treatment. Part of this lag period may be due to the necessity of slow up-titration for better tolerability. Dopamine agonists differ in their chemical structure (ergot alkaloids and non-ergots), receptor binding properties (e.g. D-2 selectivity, D-3 preference), intrinsic activity, pharmacokinetic properties (e.g. bioavailability, elimination half-life), side effect profiles, and - depending on the latter - the recommendations for dosage and dose titration. Some dopamine agonists are approved for application in early stages as monotherapy while most still are approved only as concomitant therapy in advanced parkinson's disease.