an “a Nuclear Medicine Technology and other Health Applications Treatment and Biochemical Dissection of Parkinsonism and Project Title: Allied Conditions 13. Publications: (Cont'd.) _RX¥-01-03- (a) Papavasiliou, P. S., and Cotzias, G. C, cerebrospinal fluid. Neurology (in press). Cotzias, G. C., Mena, Levodopa and dopamine in / 3d. I., and Papavasiliou, P. S, Overview of present treatment of parkinsonism with levodopa. Presented at the Symposium on Dopa Decarboxylase Inhibitors--Their Role in the Treatment of Parkinsonism, New York City, New York, November, 1972, S. T. JIYY Mena, I., Cotzias, G. C., Brown, F. C., Papavasiliou, P. S., and Miller, Defective release of growth hormone in parkinsonism improved by oD levodopa. New Engl. J. Med. 288, No. 6, 320-1 (1973), / Jd % Cotzias, G. C. Levodopa, manganese and degenerations of the ‘brain. The Harvey Lectures, Acedemic Press, New York (in press). JISUY Papavasiliou, P. S., Cotzias, G, C., Mena, gamma-hydroxybutyrate for parkinsonism. 14, ( i I., and Bell, M. J. Am. Med. Assoc. Sodium (in press). JS75 Scope: A) 200 Word Summary: The purpose of the current work is to comprehend better the mechanisms by which levodopa exercises its primary effects and side effects in patients with parkinsonism, and thus to develop even more effective management. The “off-on" phenomenon, a late defect in the chronic treatment with levodopa, - was controlled in susceptible patients either by: 1) co-administering with levodopa the peripherally acting dopa-decarboxylase inhibitor, a@-methyldopa hydrazine (MK-486); or these drugs combined, plus a moderate restriction of dietary protein intake. This latter regimen induced symptomatic stability as well as higher levels of circulating growth hormone. The possible role of this hormone in the treatment of parkinsonism is therefore studied further, The drug apomorphine, which contains a piperidine-like moiety in addition to a dopamine-like moiety in its structure, improved parkinsonism without inducing the mental aberrations expected from treatment with levodopa in’ susceptible patients. Oral administration of apomorphine, however, had induc@@.@ dose-dependent azotemia. Therefore, N-n-propylnoraporphine is tied, which is 50 times more potent than apomorphine and might theredre 1/50ch of the dose of apomorphine for oral therapy. The presence of the piperidine moiety in apomorphine suggested that piperidine should. be tried separately against mental and motor side effects of levodopa. Trials of piperidine are therefore being prepared. (See Continuation Sheet) bh V9194 RX-36