ANTIPSYCHOTIC DRUG INDUCED DYSKINESIAS

抗精神病药物引起的运动障碍

• 批准号: 6247163
• 负责人: DANIEL E CASEY
• 金额: $ 5.8万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6247163
• 关键词: Mammalia; Primates; behavioral /social science research tag; biological products; drug screening /evaluation; 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 39 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 free of neurological side effects.

抗精神病药（精神安定药）引起的神经功能障碍 运动系统的治疗存在很大的局限性。 这些 运动障碍包括急性肌张力障碍反应和药物引起的 帕金森症。 它们发生在精神安定药物治疗开始时 并且可能在许多患者的整个治疗过程中持续存在。 这些疾病的潜在药理学基础很差 明白了。 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仍保持良好 临床抗精神病疗效。 因此，学习很重要 氯氮平和其他潜在的新型抗精神病药物以确定 可能的作用机制将导致减少 神经系统副作用。 为了更好地理解这个问题，我们有 在持续几天的短期试验中研究了 39 只塞布斯猴 几个月。 影响多巴胺 D1 受体亚型的药物 并且对D2和血清素5HT1A和5HT2进行了研究。 所有这些 药物会产生肌张力障碍和帕金森病的典型症状， 氯氮平和 5HT1A 激动剂除外。 这些发现表明 氯氮平的作用机制尚不清楚。 的组合 多巴胺和血清素亚型的受体拮抗剂尚未出现 确定了一条明确的药物开发路线，以创造新的药物 没有神经副作用的抗精神病药物。