ANTIPSYCHOTIC DRUG INDUCED DYSKINESIAS

抗精神病药物引起的运动障碍

• 批准号: 6277340
• 负责人: DANIEL E CASEY
• 金额: $ 7.52万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277340
• 关键词: Mammalia; Primates; biological products; drug /agent; mental disorders; nervous system; psychology

Antipsychotic (neuroleptic) drug-induced neurological dysfunctions in the motor system are substantial limitations of therapy. These motor disorders include acute dystonic reactions and drug-induced parkinsonism. They occur at the initiation of neuroleptic treatment and may continue in many patients throughout the course of treatment. The underlying pharmacological basis of these disorders is poorly understood. A recently developed drug, clozapine, appears to have very few of these neurological side effects, yet maintains good clinical antipsychotic efficacy. Therefore, it is important to study clozapine and other potentially new antipsychotic drugs to identify the possible mechanism of action that will lead to reduced neurological side effects. To better understand this issue, we have studied 35 cebus monkeys in short-term trials lasting a few days to a few months. Drugs which affect the receptor subtypes of dopamine D1 and D2 and serotonin 5HT1A and 5HT2 have been studied. All these drugs produce typical signs of dystonia and parkinsonism, with the exception of clozapine and 5HT1A agonists. These findings suggest that the mechanism of clozapine is as yet unknown. Combinations of receptor antagonists of dopamine and serotonin subtypes have not yet identified a clear line of drug development to pursue for creating new antipsychotic drugs that are free of neurological side effects.

抗精神病药（神经肌动蛋白）药物诱导的神经功能障碍 在运动系统中是治疗的重大局限性。 这些 运动障碍包括急性肌张力反应和药物诱导 帕金森主义。 它们发生在启动神经治疗 在整个治疗过程中，许多患者可能会继续进行。 这些疾病的基础药理学基础很差 理解。 最近开发的药物氯氮平似乎具有 这些神经系统副作用很少，但保持良好 临床抗精神病药。 因此，研究很重要 氯氮平和其他潜在的新抗精神病药以识别 可能导致减少的作用机制 神经副作用。 为了更好地理解这个问题，我们有 在短期试验中研究了35只Cebus猴子，持续了几天 几个月。 影响多巴胺D1受体亚型的药物 已经研究了D2和5-羟色胺5HT1A和5HT2。 所有这些 药物会产生肌张力障碍和帕金森氏症的典型迹象， 氯氮平和5HT1A激动剂的例外。 这些发现表明 氯氮平的机制尚不清楚。 组合 多巴胺和5-羟色胺亚型的受体拮抗剂尚未 确定了一条明确的药物开发线，以创建新的 没有神经副作用的抗精神病药。