New delivery techniques in the drug treatment of Parkinson's disease

✍ Scribed by W. Poewe

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 66 KB
• Volume: 7
• Category: Article
• ISSN: 0885-3185
• DOI: 10.1002/mds.870070517

✦ Synopsis

A marked response to oral dopaminergic substitution is one of the diagnostic criteria for idiopathic Parkinson's disease. Oral L-Dopa treatment remains to be the most efficacious and best tolerated way of parkinsonian drug therapy. A majority of patients, however, will develop late complications including abnormal drug-induced involuntary movements and oscillations in motor response after sustained L-Dopa monotherapy for more then 5 years. Pathophysiological mechanisms underlying such phenomena of L-Dopa late failure are incompletely understood but seem to include central pharmacokinetic alterations associated with disease progression as well as pharmacodynamic receptor changes in the doparnine system. The latter may be due to chronic pulsatile striatal doparnine receptor stimulation induced by repetitive peak and troughs of striatal dopamine concentration following periodic oral dosing of L-Dopa. Experimental as well as therapeutic clinical studies of continuous dopaminergic stimulation via i.v. or intrajejunal levodopa infusions or subcutaneous agonist infusions have been shown to alter such secondary dopamine receptor pharmacodynamic sensitivity. Clinically this is associated with smoothing out of response fluctuations and changes in dopamine receptor sensitivity leading to decreased dose requirements and/or lessened degrees of dyskinesias. As a consequence new drug delivery techniques for dopaminergic drugs in Parkinson's disease focus on modes of continuous drug delivery. Long-term experience with continuous S.C. infusions of apomorphine indicates sustained responsiveness at stable dose levels with greatly reduced motor fluctuations and progressive reduction of interdose dyskinesias in some patients (1,2,3). Similar results havfe been reported for chronic enteral infusions of L-Dopa (5). New modes of antiparkinsonian drug delivery include transdermal systems, long-acting oral DA agonists and implantable polymeric drug-reservoirs ( 4 ) .