BIOCHEMISTRY AND PHARMACOLOGY OF TRACE AMINES IN BRAIN

我们提案的第一个目标是确定各种因素的比例 实验动物尿胺代谢起源于 中枢神经系统。 要研究的代谢物包括 儿茶酚胺和微量胺的酒精代谢物。 这些代谢物的浓度将同时测定 我们开发的气相色谱-质谱技术 在我们的实验室。 特别感兴趣的两种代谢物是 3,4-二羟基苯乙醇和对羟基苯乙二醇，代谢物 我们分别鉴定并发现了多巴胺和章鱼胺 在大鼠大脑和尿液以及人类中大量存在 尿液。 我们的研究应该为使用浓度提供基础 各种胺代谢物作为资产周转率的有用指标 实验动物大脑中以及体内相应的胺 人类受试者，并用于识别胺中可能的干扰 新陈代谢可能是各种精神疾病的基础或结果 神经系统疾病，例如抑郁症和帕金森病。 的 第二个目标是应用这些程序来调查 各种氨基酸前体转化为相应的胺。 例如，我们将确定合成氨基酸的程度 章鱼胺的前体，对羟基苯基丝氨酸，被转化为章鱼胺 及其代谢。 这些研究可以表明这种氨基酸是否 可用作选择性增加章鱼胺的药理学工具 的形成，以阐明其可能的神经化学作用以及 它可能与大脑功能障碍有关。 最后，效果如下 典型和非典型的急性和慢性给药 将研究抗抑郁药对脑胺代谢的影响。 特别是， 我们将测试这样一种观点：章鱼胺或其他物质的水平增加 微量胺是多种抗抑郁药的共同特征，可能 充当这些药物延迟效应的触发因素。

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.