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