Nuclear Medicine Technology and other Health Applications
Project Title:
17,
Treatment and Biochemical Dissection of Parkinsonism and
RX-01-03-(3)
Allied Conditions
Expected Results in FY 1974:
Continuation of studies on cholinergic agents in mice is planned in
order to prepare for human investigations.
The studies on manganese metabolism will be continued on animals and
extended in man by using Mn isotopes (Mn-54) which it is hoped will serve
as a possible indicator of cerebral sensitivity to neuractive drugs.
The
possibility that injected dopamine may be caused to enter the brain by
inhibiting its deamination encourages the use of C-11 labeled dopamine as
an agent which may allow visualization of intracerebral structures.
If
successful in imaging brains of large animals this approach will be extended
to humans,
-*f
As indicated above oral. apomorphine proved to be an effective dopaminergic
agent for the control of parkinsonism,
With the exception of reversible
azotemia induced by high doses of apomorphine it appears safe and induces
no dyskinesia or mental aberration.
A newly synthesized analogue, N-n-propyl-
noraporphine is reported to be about 50 times more effective as a dopaminergic
agent than apomorphine. This agent will be given to parkinsonian patients
in therapeutic trials anticipating beneficial effects on the extrapyramidal
system and no induction of azotemia,
|
Analogues of apomorphine are being synthesized by combining a catechol
moiety with that of a piperidine.
Such analogues are potentially dopaminergic
with activity increased by alkyl substituents on the piperidine.
Spectrofluorimetric and radioassays are being developed for tracing the metabolic
pathways of these analogues.
The work on pharmacological psychoses will be extended from the
physostigmine experiments to other direct neuronal cholinergic stimulators
not only in parkinsonism but also in investigations of potential treatments
of other pharmacological mental aberrations.
Proposed agents include
piperidine and analogues and oxotremorine.
In collaboration with Dr. S. H. Cohn the endogenous release of growth
hormone by levodopa administration will be pursued as a potential treatment
of osteoporosis.
18.
Expected Results in FY 1975:
Studies will continue with emphasis determined by findings chat develop
as the work progresses.
(See Continuation Sheet)
1119200
.
RX-42