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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