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Dopamine agonists:
what is the place of the newer compounds in the treatment of PD?

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 developing 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.

J Neural Transm Suppl 1999;55:33-45
Rascol O
Department of Clinical Pharmacology, University Hospital, Toulouse, France.
PMID: 10335491, UI: 99267972
http://www.ncbi.nlm.nih.gov/

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janet paterson   52 now 41 dx 37 onset  [log in to unmask]
613-256-8340   PO Box 171  Almonte  Ontario  K0A 1A0  Canada
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