Investigational drugs

This chapter provides an overview of the new pharmacological strategies in Parkinson's disease (PD). Levodopa (LD) is considered the mainstay of treatment of Parkinson's disease (PD). However, LD has not been shown to slow the progression of the disease, and PD patients face major shortcomings in the chronic phase of the disease. Fluctuations and levodopa-induced dyskinesia (LID) are the major complications in the current therapeutic approach to the treatment of PD, significantly affecting patient's quality of life. The dopamine agonists, which are compounds with a better pharmacokinetic profile than LD, are also well established. Dopamine agonists can alleviate Parkinsonian symptoms in previously untreated patients with a much reduced incidence of fluctuations and dyskinesia. Chronic use of dopamine agonists is also associated with frequent psychiatric side-effects, including visual hallucinations, delusions, and paranoid psychosis. Several strategies are proposed and developed in order to improve the pharmacokinetics and pharmacodynamics of various drugs used in PD. Therapeutic research in the future is expected to be moving in several different directions. Among these are: (1) development of neuroprotective drugs, capable of blocking or at least slowing down the degenerative process responsible for neuron death, or even of restorative strategies, which would allow normal brain function to be regained, (2) further improvement in the replacement of dopaminergic loss, (3) antidyskinetic drugs, and (4) symptomatic drugs acting on neurotransmitters other than dopamine, or which may target the brain in other areas rather than only in the striatum.