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