DRUG-TREATMENT OF PARKINSONS-DISEASE IN THE 1990S - ACHIEVEMENTS AND FUTURE POSSIBILITIES

Advances in the medical treatment of Parkinson's disease have improved the disability related to complications of long term levodopa therapy , including motor fluctuations, dyskinesias and neuropsychiatric toxic ity. A range of new dopamine agonists are in various stages of preclin ical and clinical development. Cabergoline appears to be effective in improving moderate motor fluctuations, and a number of dopamine partia l agonists that can act as either agonists or antagonists depending on the degree of denervation and receptor sensitivity are being investig ated. Apomorphine represents a significant advance in the treatment of well developed motor fluctuations in selected patients who are able t o master the technique of subcutaneous administration. The catecholami ne-O-methyl transferase inhibitors are proving useful in phase III stu dies in the management of patients with moderate motor fluctuations. A role for glutamate antagonists is supported by animal and early clini cal data, although the poor therapeutic index associated with the curr ently available nonselective, noncompetitive glutamate antagonists has prompted a search for more selective antagonists with less toxicity. The management of levodopa-induced dyskinesias remains a major therape utic challenge. Some reports of dopamine partial agonists, selective D -2 receptor antagonists and atypical antipsychotics being useful await confirmation. Neuropsychiatric toxicity probably remains the major do se-limiting adverse effect of levodopa and is a major reason for parki nsonian patients being admitted to nursing homes. The development of n ew atypical antipsychotics with improved therapeutic indices, along wi th the possible use of serotonergic antagonists, may improve managemen t of this difficult problem. The challenge will be to fit these new fo rms of treatment into our present range of available drugs and to asse ss their relative role within the emerging framework of functional neu rosurgery for parkinsonian disability.