CURRENT AND EMERGING STRATEGIES IN THE MANAGEMENT OF PARKINSONS-DISEASE - A CRITICAL REAPPRAISAL

The pharmacological treatment of Parkinson's disease (PD) can be subdi vided into symptomatic treatment (e.g. levodopa combined with a periph eral decarboxylase inhibitor (PDI), direct-acting dopamine receptor ag onists, amantadine, centrally acting antimuscarinic drugs and catechol -O-methyltransferase (COMT) inhibitors) aimed at restoring striatal do pamine function and reversing functional disability, and neuroprotecti ve treatment (e.g. monoamine oxidase-B (MAO-B) inhibitors) aimed at in terfering either with the cause of the disease or pathophysiologic mec hanism of substantia nigral cell death. Despite the controversy about the development of long-term side effects levodopa/PDI remains the gol d standard for the symptomatic treatment of PD. Direct-acting dopamine receptor agonists are usually recommended as adjuvants to levodopa/PD I. There is no compelling evidence that newer generation dopamine rece ptor agonists have a greater therapeutic effect than existing ones. Am antadine has limited effectiveness and loss of its beneficial effect a fter several months seriously limits its usefulness. Centrally-acting antimuscarinic drugs all have low efficacy and high toxicity and shoul d be restricted for young patients with tremor-predominant PD. COMT in hibitors improve the pharmacokinetic properties of levodopa, however d ata are still lacking about their long-term efficacy and safety. The n europrotective effect claimed by MAO-B inhibitors can well be offset b y the increased mortality reported in patients treated with these drug s. The clinical and pharmacokinetic properties of the current and emer ging drugs used in the treatment of PD are reviewed and guidelines are provided for the management of early and advanced PD.