PMID: 9337447: New pharmacotherapy for PD

[janet paterson <janet313@xxxxxxxxxxx>]

New pharmacotherapy for Parkinson's disease.

OBJECTIVE: To summarize the development, pharmacology, pharmacokinetics, 
efficacy, and safety of five investigational antiparkinsonian drugs that are in 
or have recently completed Phase III trials:

three dopamine agonists,
pramipexole,
ropinirole,
cabergoline;

two catechol-O-methyltransferase (COMT) inhibitors,
entacapone
tolcapone.

The pathophysiology and the role of dopamine in Parkinson's disease are also 
reviewed.

DATA SOURCES: A MEDLINE search of relevant English-language literature, 
clinical studies, abstracts, and review articles pertaining to Parkinson's 
disease was conducted. Manual searches of 1996/1997 meeting abstracts published 
by the American Academy of Neurology and the Movement Disorders Society were 
also performed.

Manufacturers provided unpublished Phase III trial efficacy and pharmacokinetic 
data.

STUDY SELECTION AND DATA EXTRACTION: Clinical trial investigations selected for 
inclusion were limited to human subjects.

Interim analyses after 6 months for long-term clinical studies in progress were 
included.

Pharmacokinetic data from animals were cited if human data were unavailable.

Statistical analyses for all studies were evaluated.

DATA SYNTHESIS: By selectivity targeting D2 receptors, the newer dopamine 
agonists (i.e., cabergoline, pramipexole, ropinirole) may delay the 
introduction of levodopa and thus the occurrence of levodopa-induced 
dyskinesias.

In addition, they are efficacious as adjunctive therapies in patients with 
advanced Parkinson's disease.

Unlike the currently available dopamine agonists, pramipexole and ropinirole 
are non-ergot derivatives and do not cause skin inflammation, paresthesias, 
pulmonary infiltrates, or pleural effusion.

The COMT inhibitors, tolcapone and entacapone, improve the pharmacokinetics of 
levodopa by preventing its peripheral catabolism and increasing the 
concentration of brain dopamine; thus, these agents may reduce the incidence of 
"wearing-off" effects associated with the short half-life of levodopa and the 
progression of Parkinson's disease.

CONCLUSIONS: Interim 6-month analyses of pramipexole, ropinirole, and 
cabergoline for symptomatic treatment of early Parkinson's disease have shown 
these drugs to be efficacious and relatively well-tolerated when used as 
monotherapy.

Their role in delaying the development of motor fluctuations and delaying the 
addition of levodopa is the subject of long-term clinical studies.

In advanced stages of Parkinson's disease, these medications were also 
efficacious; however, the main adverse effects included dyskinesias, 
somnolence, and hallucinations.

The COMT inhibitors, entacapone and tolcapone, have also demonstrated efficacy 
in improving on-time in patients with stable disease.

Tolcapone has also demonstrated efficacy in patients with motor fluctuations.

Both drugs are relatively well-tolerated, with the exception of dyskinesias 
that require reduction of the levodopa dosage and occasional diarrhea.


Ann Pharmacother 1997 Oct;31(10):1205-17
Gottwald MD, Bainbridge JL, Dowling GA, Aminoff MJ, Alldredge BK
University of California, San Francisco California 94143 USA
PMID: 9337447, UI: 97478604

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janet paterson
52 now / 41 dx / 37 onset
613 256 8340 po box 171 almonte ontario canada K0A 1A0
a new voice: <>
<janet313@xxxxxxxxxxx>