Nuclear Medicine Technology and other Health Applications Treatment and Biochemical Dissection of Parkinsonism and Project Title: Allied Conditions RX-01-03-(a) 14, Scope: (Cont'd.) B) Supplement to 200 Word Summary: The objectives remain the study and cerrection of biochemical defects of extrapyramidal diseases which were treated first with levodopa alone and later with a combination of levodopa and the decarboxylase inhibitor | a-methyldopa hydrazine (MK-486), Definition of the precise mechanism of the short-lived episodic dimunition of the treatment's effectiveness and of the involuntary movements and mental side-effects is sought. Since dopamine, the active metabolite of dopa, administered systemically does not cross the blood-brain barrier in sufficient amounts to elicit cerebral effects, apomorphine, a dopaminergic tertiary amine, is used in order to study dopaminergic effects on the central nervous system, The therapeutic effects of apomorphine are similar to those of levodopa whereas most side-effects are less. Oral apomorphine, however, induced an apparently dose-dependent azotemia; its analogue, N-n-propylnoraporphine, which requires 1/50th the dose of apomorphine, is now studied. Dietary and hormonal factors influence the effects of levodopa. There is particular interest in exploring the role of growth hormone (GH) in man; also the effect of levodopa is potentiated by growth hormone in animals. Since this hormone is investigated as a treatment of osteoporosis, the total-body neutron activation analysis technique described in RX-01-01-(b) is used to study changes in total-body calcium of parkinsonians receiving levodopa, In animals, the use of monoamine oxidase inhibitors to prevent the destruction of dopamine demonstrated that its cerebral effects are similar to those of levodopa. One might be able therefore to utilize : metabolic inhibitors to promote the entrace of C-ll-dopamine into the brain and thus develop a method for scanning intracerebral structures, The discoveries of various interactions between dopamine and manganese led to development of a nondestructive analysis for manganese permitting subsequent analysis for dopamine in the same biological sample. Application of this method to regional samples of cat brains is in progress. Furthermore, manganese radioisotopes have permitted the evaluation of the cerebral reactions of animals to levodopa and thus Mn-54, used as a marker may enable prediction of cerebral reactivity to drugs such as levodopa, 15. Mpjationship to Other Projects: Wee extensive investigations stimulated by the introduction of levodopa for. the treatment of parkinsonism have been extended toother extrapyramidal disorders and have stimulated a search for newer and better drugs by numerous other centers, The neurochemical studies that evolved have branched out more recently to studies of hormonal interactions as well as pituitary-tropic inhibiting factors as modifiers of the effects of dopaminergic drugs. (See Continuation Sheet) VET9E9S RX-37