Methods and Findings in Experimental and Clinical Pharmacology
Vol. 25, Suppl. A, 2003
ISSN 0379-0355
Copyright 2003 Prous Science, S.A.
CCC: 0379-0355/2003
http://www.prous.com

Advances in the Pharmacology and Treatment of Parkinson's Disease

P. Jenner

Neurodegenerative Diseases Research Centre, King's College, London, UK

The current dopaminergic treatment of Parkinson's disease (PD) is highly effective in the early stages of the illness, but chronic treatment leads to a loss of drug efficacy, dyskinesia induction and psychosis. In addition, many non-motor components of PD, such as postural instability, do not respond to available therapy. Consequently, there is a need for a new generation of pharmacological agents able to provide long-term benefit while avoiding common side-effects of treatment.

New dopaminergic approaches to PD are currently under development. Drugs that act as D_l receptor agonists, dopamine reuptake blockers and partial D₂ agonists offer symptomatic benefit in PD without the unwanted actions currently encountered. For example, D_l agonists should be anti-parkinsonian without inducing dyskinesia or provoking psychosis, while avoiding nausea, vomiting, hypotension and endocrine changes. New means of delivering dopaminergic drugs, including buccal and sublingual preparations, and perhaps most excitingly, a transdermal patch, are currently undergoing clinical evaluation. Therapeutic strategies providing continuous dopaminergic stimulation are being employed to prevent dyskinesia development and to reverse established dyskinesia in later stage patients.

However, there is currently major interest in targeting non-dopaminergic receptor systems within basal ganglia that are beyond the damaged nigro-striatal pathway. Indeed, there is a wide range of other transmitter systems within basal ganglia capable of modulating motor function in PD. The drugs being produced include glutamate antagonists, adenosine antagonists, a-adrenergic antagonists and 5-HT agonists. These compounds can alleviate the motor symptoms of PD, avoid or prevent dyskinesia induction or suppress established involuntary movements.

The future treatment of PD will see an improvement over current therapy with drugs effective during all stages of the illness. The treatment related complications that limit therapy in late stage patients may be overcome and aspects of PD that are presently untreatable may be controlled. However, it is inevitable that new pharmacological approaches will bring their own problems and a new range of unwanted side-effects.

Methods and Findings in Experimental and Clinical Pharmacology Vol. 25, Suppl. A, 2003
ISSN 0379-0355 Copyright 2003 Prous Science, S.A. CCC: 0379-0355/2003 http://www.prous.com