Dopamine agonists: what is the place of the newer compounds in the treatment of Parkinson's disease?

Three new dopamine agonists (cabergoline, pramipexole, ropinirole) have been put on to the market within the past months to treat patients with Parkinson's disease. Like any marketed dopamine agonists, the new compounds bind to the D2-like receptors. Pramipexole and ropinirole appear to be quite close drugs. Both are selective non ergot D2 (and preferentially D3) agonists, with an elimination half-life of 5 to 10 hours. Conversely, cabergoline is an ergot derivative, less selective for the D2 receptors, with a much longer elimination half-life (60 hours or more). In moderately advanced levodopa treated patients with Parkinson's disease and motor fluctuations, cabergoline, pramipexole and ropinirole all do significantly better than placebo in reducing UPDRS motor examination scores, time spent off and daily dose of levodopa. None of the 3 newer agonists proved to do significantly better than bromocriptine in this indication, at the cost of very similar adverse effects. In de novo levodopa naive patients, pramipexole and ropinirole did significantly better than placebo in short-term (few months) follow-up trials, at the cost again of classical dopaminergic adverse effects. Ropinirole was marginally more effective than bromocriptine, while its use induced the same risk of psychosis than the "old" reference agonist. Early treatment with cabergoline, compared with levodopa, in a long-term (5 year) study reduced the relative risk of developping motor complication by more than 50%. A similar study is presently on-going to compare ropinirole and levodopa. Clinical trials to assess putative neuroprotective effects are also on going with ropinirole and pramipexole. Up to now, the available clinical controlled data suggest that the newer dopamine agonists have very similar clinical effects with only minor superiority, if any, versus bromocriptine.