Adverse effects of antiparkinsonian drugs.

In the last decade neurohormone replacement therapy with levodopa has revolutionised the treatment of Parkinson's disease. At the same time the use of amantadine and dopamine-like ergot drugs has developed, although there is still a place for anticholinergic drugs, not in use for a century. These advances have resulted in the availability of many different drugs to treat Parkinsonism with different pharmacological actions. It is now usually possible to control disability, at least in the initial stages of disease, although sometimes at the expense of frequent and disabling side effects. In most cases these result from the widespread distribution of cholinergic and dopaminergic systems inside and outside the brain and the non-selective action of therapeutic agents on these different systems. Despite the recent division of dopamine receptors into D1 and D2 classes, no selective dopamine-like antiparkinsonian drugs are known. The practical treatment of Parkinsonism depends on accurate knowledge of the side effects as well as therapeutic effects of many different drugs, and requires titration of individually determined dosages in different patients to achieve the optimum response. This is usually determined by dose-limiting side effects as well as by improvement. The possibility that the eventual development of response fluctuation and failure may result from the sustained use of large doses of dopamine-like drugs must be considered, and it is probably wise at present to give low rather than high doses of the agents. No presently available treatment appears to influence the natural progression of Parkinsonism.