Selective dopamine agonists In man and the mptp-treated primate model.

A thesis submitted to the Faculty of Medicine, University of the Witwatersrand, Johannesburg, for the degree of Doctor of Philosophy (Medicine)Idiopathic Parkinson's disease remains one of the commonest neurodegenerative diseases known today. It causes incapacita ting symptoms untreated but when given replacement neurotransmitters, principally levodopa or dopamine, corrects the major features of the illness. The fundamental cause of nigral dopaminergic cell decline remains unknown, is not principally genetic, but may be due to abnormal hepatic handling of neurotoxins. One such putative neurotovin is MPTP which causes parkinsonism in man and primates. The MPTP-treated primate model is thus a useful model within which new drugs, including dopamine receptor agonists may be tested. Levodopa remains the mainstay of successful pharmacotherapy in the treatment of parkinson's disease. However the last decades have taught us that levodopa treatment with time produces problems of dyskinesias and unpredictable motor fluctuations. Hence alternate pharmacotherapy is sought to supplement levodopa or possibly to circumvent its necessity. (Abbreviation abstract)Andrew Chakane 201