BIOCHEMISTRY AND PHARMACOLOGY OF TRACE AMINES IN BRAIN

我们建议的第一个目标是确定各种比例

The first goal of our proposal is to determine what proportion of various urinary amine metabolities in experimental animals originates in the central nervous system. The metabolites to be studied include the alcoholic metabolites of catacholamines and of trace amines. Concentrations of these metabolites will be determined simultaneously using gas chromatographic-mass spectrometric techniques which we have developed in our laboratory. Two metabolites of particular interest are 3,4-dihydroxyphenylethanol and p-hydroxyphenylglycol, metabolites of dopamine and octopamine, respectively, that we have identified and found to be present in significant quantities in rat brain and urine and in human urine. Our studies should provide a basis for using concentrations of various amine metabolites as useful indicators of the turnover rate of the corresponding amines in the brain of experimental animals as well as in human subjects, and for identifying possible disturbances in amine metabolism that may underlie or result from various psychiatric and neurological illnesses, such as depression and Parkinson's disease. The second goal is to apply these procedures to investigate the extent to which various amino acid precursors are converted to the corresponding amines. For example, we will determine to what extent the synthetic amino acid precursor of octopamine, p-hydroxyphenylserine, is converted to octopamine and its metabolities. These studies could indicate whether this amino acid may be used as a pharmacological tool to selectively increase octopamine formation, in order to elucidate its possible neurochemical role as well as its possible involvement in brain dysfunction. Finally, the effects of both acute and chronic administration of typical and atypical antidepressants on brain amine metabolism will be studied. In particular, we will test the notion that an increased level of octopamine or other trace amines is a common feature of diverse antidepressant agents and may serve as a trigger to the delayed effects of these drugs.