DEBRISOQUIN AS AN AGENT FOR STUDY OF PSYCHOTIC STATES

DEBRISOQUIN 作为精神状态研究的药物

• 批准号: 3379497
• 负责人: JAMES W MAAS
• 金额: $ 19.04万
• 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/3379497
• 关键词: 3 methoxy 4 hydroxyphenylethyleneglycol; MAO inhibitors; antipsychotic agents; clonidine; dopamine; haloperidol; homovanillate; 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/精神病患者和对照者将进行交叉研究 截面和纵向设计来评估是否去甲肾上腺素能 这些患者的活动量增加。去甲肾上腺素的代谢物 特别要研究的是VMA、去甲变肾上腺素和MHPG。我们也会 查看脑脊液中去甲肾上腺素和代谢物的水平。的运作 通过测量尿液中的 HVA 和 DOPAC 来评估多巴胺系统， 血浆和脑脊液。一般假设是去甲肾上腺素能系统 精神分裂症患者过度活跃，并且精神分裂症/精神病是 其特征是去甲肾上腺素和/或其水平升高 所有体液中的代谢物，并且代谢物的水平也增加 血浆 HVA 不增加总 DA 合成（尿液 HVA）。 神经递质代谢物将在患者断断续续的情况下进行研究 异喹啉 (DBQ) 以及使用任一抗精神病药物治疗期间 （氟哌啶醇）或 α2 激动剂可乐定。我们将使用 DBQ，因为它已经 单胺氧化酶抑制活性但不渗透大脑。经过 减少 DA 和 NE 代谢物的外周贡献 尿液和血浆中使用它会产生多巴胺的代谢物，也许 血浆和尿液中的去甲肾上腺素更好地反映了活性和 中枢神经系统中胺代谢物的浓度 没有药物。 DBQ 的这种使用在我们之前的实践中已被证明非常有价值 研究。这项工作的长期目标是了解 精神分裂症/精神病中的 NE 系统，并将这些知识应用于 改进治疗的设计。这项与 DBQ 的拟议工作是 继续和扩展我们的研究计划可能会产生 有关当前和未来诊断和治疗的临床有用信息 精神分裂症患者的治疗工作。