DEBRISOQUIN AS AN AGENT FOR STUDY OF PSYCHOTIC STATES

DEBRISOQUIN 作为精神状态研究的药物

• 批准号: 3379502
• 负责人: JAMES W MAAS
• 金额: $ 21.41万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3379502
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; MAO inhibitors; antipsychotic agents; clonidine; debrisoquin; dopamine; haloperidol; homovanillate; human subject; longitudinal human study; mental disorder diagnosis; mental disorders; neurotransmitter metabolism; norepinephrine; normetanephrine; schizophrenia

Schizophrenic/psychotic patients and controls will be studied in a cross sectional and longitudinal design to evaluate whether noradrenergic activity is increased in these patients. The metabolites of norepinephrine specifically to be studied are VMA, normetanephrine and MHPG. We will also look at levels of norepinephrine and metabolites in CSF. The functioning of the dopamine system will be assessed by measuring HVA and DOPAC in urine, plasma and CSF. The general hypotheses are that noradrenergic systems are hyperactive in schizophrenic subjects and that schizophrenia/psychosis is characterized by an increased level of norepinephrine and/or its metabolites in all body fluids and that there is also an increased level of plasma HVA without an increase in total DA synthesis (urine HVA). Neurotransmitter metabolites will be studied with patients on and off debrisoquin (DBQ) and during treatment with either neuroleptics (haloperidol) or the alpha2 agonist clonidine. We will use DBQ as it has monoamine oxidase inhibiting activity but does not penetrate brain. By reducing the peripheral contribution of metabolites of DA and NE present in urine and plasma its use results in the metabolites of dopamine and perhaps norepinephrine in plasma and urine better reflecting the activity and concentrations of amine metabolites in the central nervous system than without the drug. This use of DBQ has proven quite valuable in our prior studies. The long-term goal of this work is to understand the role of the NE system in schizophrenia/psychosis and to apply this knowledge to the design of improved treatments. This proposed work with DBQ is a continuation and extension of our program of research that may yield clinically useful information regarding present and future diagnostic and treatment efforts with schizophrenic patients.

精神分裂症/精神病患者和对照组将进行交叉研究。 截面和纵向设计，以评估是否去甲肾上腺素能 这些患者的活动增加。去甲肾上腺素的代谢物 具体研究的是VMA、去甲肾上腺素和MHPG。我们还将 看看脑脊液中去甲肾上腺素和代谢物的水平的运作 通过测量尿中的HVA和DOPAC来评估多巴胺系统， 血浆和CSF。一般的假设是去甲肾上腺素能系统是 精神分裂症/精神病在精神分裂症受试者中过度活跃， 其特征在于去甲肾上腺素和/或其 所有体液中的代谢物，也有增加的水平， 血浆HVA而不增加总DA合成（尿HVA）。 神经递质代谢物将与患者进行研究， 异喹胍（DBQ）和在使用精神抑制剂治疗期间 （氟哌啶醇）或α 2激动剂可乐定。我们将使用DBQ 单胺氧化酶抑制活性，但不渗透脑。通过 减少外周的DA和NE代谢物的贡献， 尿液和血浆中，它的使用导致多巴胺的代谢产物， 血浆和尿液中的去甲肾上腺素更好地反映了活性， 中枢神经系统中胺代谢物的浓度比 没有药物。DBQ的这种使用在我们以前的研究中已经证明是非常有价值的。 问题研究这项工作的长期目标是了解 NE系统在精神分裂症/精神病中的作用，并将这些知识应用于 设计更好的治疗方法。与DBQ的这项拟议工作是一个 继续和扩展我们的研究计划， 关于当前和未来诊断和 精神分裂症患者的治疗