Nuclear Medicine Technology and other Health Applications Project Title: 15. Treatment and Biochemical Dissection of Parkinsonism and RX-01-03-(a) Allied Conditions Relationship to Other Projects: (Cont'd.) Parkinsonism is being studied intensely by Dr. A. Barbeau in Montreal; by Dr. M. Yahr at Columbia; by Dr. F,. McDowell at Cornell; by Dr. A. Battista at N.Y.U.; and many other leaders of groups elsewhere. Neurochemical work is being performed in so many excellent centers that it is impossible to choose even representative examples. Related studies at BNL include those using total body neutron activa- tion analysis as reported in RX-01-01-(b) and utilization of C-1l-dopamine as reported in RX-01-03-(c). Dr. Kraner of the BNL Instrumentation Division contributes essentially to the development of instrumentation in this project. 16. Technical Progress in FY 1973: ' 4 a-methyldopa hydrazine. (MK-486) in combination with levodopa emerges as a most useful therapeutic tool as a consequence of inhibiting the catabolism of levodopa exclusively in peripheral tissues. It has lowered the dose requirements of levodopa by approximately 80%, while it has induced more rapid therapy, better diurnal symptomatic control, and a new capability to co-administer pyridoxine with impunity in patients receiving levodopa. Its main disadvantage is the rapid induction of involuntary movements. Fixed combinations of levodopa with MK-486 and a multiple dose schedule were proposed for the successful application by practitioners of this new form of therapy ~“. for parkinsonism, Despite previous publications to the contrary, melatonin did not affect the signs of parkinsonism, the therapeutic effects of levodopa, or adventitious movements. A tranquilizing effect was encountered, therefore suggesting that melatonin be tried for manic-depressive disorders. Although animal experiments with nicotinamide were found encouraging, clinical trials proved the vitamin to be ineffective in controlling dopa-induced involuntary movements in patients. Similarly, although many theoretical considerations and animal experiments suggested that L-meta-tyrosine would show improvement of parkinsonism there was no demonstrable improvement observed. It was concluded from these experiments, however, that the catechol or an equivalent configuration is necessary, since this is the only difference between L-metatyrosine and L-dopa. cted apomorphine was found to be effective against tremor, rigidity, and cfepisodin bradykinesia when given both alone and with oral levodopa. Yet, Me dopa induced "awakening effect", the dyskinesia and the nausea were often ahtagonized by apomorphine whereas the sedative effects and nausea of apomorphine were antagonized by levodopa. The coexistence of both synergistic and antagonistic effects between the two drugs may be a result of the structure of apomorphine, a hybrid drug by virtue of containing several neuro-active moieties. Slow administration of oral apomorphine to 14 patients up to dosages of 1.5 g/d induced more of the expected side effects, while significant improvement of the parkinsonism was induced in five patients. Unexpectedly, three patients exhibited a reversible marked elevation of (See Continuation Sheet) Lh 191496 RX- 38