Q OS C ‘ Nuclear Medicine Technology and other Health Applications Treatment and Biochemical Dissection of Parkinsonism and Project Title: Allied Conditions 16. Technical Progress in FY 1973: BX-01-03- (8) (Cont'd.) both blood urea nitrogen and blood creatinine levels. trials be conducted with N-n-propylnoraporphine. This suggests such In studies on synthesis of tritium- and deuterium-labeled apomorphine, tritiated apomorphine was synthesized from morphine and from apomorphine co, we by labeling the two aromatic rings and will be used in future animal experimentation, The reported work showed how exclusive labeling of the catechol ring can be achieved by controlling the reaction conditions. In response to work of others heralding iatrogenic acromegaly in patients receiving levodopa it was found that: 1) spontaneous releases of growth hor- mone, similar to those evoked by levodopa were found normally during sleep, 2) none of 105 patients with parkinsonism or chronic manganese poisoning treated here have developed acromegaly, 3) large pulses of circulating growth hormone were found only aftér the morning dose of levodopa, 4) life-long oN consumption of levodopa has prolonged the lives of mice. In preliminary observations of untreated patients with parkinsonism there was a virtual absence of the circadian rises of growth hormone in contrast to normals in whom several large rises of hormones were spontaneously apparent, The relative inability of the parkinsonian patients to raise growth hormone levels beyond the basal ones seems to be corrected by levodopa. This study is continuing with a larger number of patients and growth hormone levels will be correlated with patient performance. In studies of the effects of protein metabolism in parkinsonism it was shown, in mice, that agents which inhibit protein synthesis diminish the cerebral effects of levodopa. This result is complementary to the observation that drugs reputed to increase protein synthesis increase the duration and intensity of these effects. Inhibitors of protein synthesis also diminished the effects of apomorphine and oxotremorine whereas inactive analogues did not. The findings suggest that proteins critical to the function of dopa- minergic and cholinergie receptors undergo rapid turnover. Some patients reported episodic losses of the therapeutic effects of levodopa following a high protein meal. Since levodopa, a large neutral amino acid, might compete with dietary amino acids for transport into the brain, isocaloric diets were administered with varying protein content and the effects on symptomatic stability determined, These studies suggest the following: 1) ne logical effects became evident in most patients with variation of the ceec were most striking when levodopa was administered alone; 2) high prote Antake tended to cancel both the therapeutic effects and the side effect ®of levodopa, 3) low protein diets tended to potentiate and stabilize the therapeutic effects, 4) the fewer the meals, the greater the instability. These results indicate that long-term studies of low protein intakes are in order, ( (See Continuation Sheet) b179t9) RX-39