EXTRACT OF SAURURUS WITH NEUROLEPTIC ACTIVITY

具有神经抑制活性的三白龙提取物

• 批准号: 3375772
• 负责人: KAMARSU V RAO
• 金额: $ 5.96万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 1982
• 资助国家: 美国
• 起止时间: 1982-09-28 至 1987-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3375772
• 关键词: amphetamines; apomorphine; aquatic biology; chemical structure function; lignans; norepinephrine; plant extracts; stereochemistry; tranquilizer; tryptamines

The extract of Saururus cernuus (a toxic aquatic weed) on fractionation gave a series of ten closely related compounds (SC-1, SC-2 ...) which appear to belong to the class of neolignans. Of these, SC-5, 7, 8 and 9 represent the toxic principles, with SC-8 being the major component. At nontoxic doses, SC-8 showed behavioral patterns in mice typical of a major tranquilizer. In further preliminary testing, it inhibited aggressive response and amphetamine-induced stereotypy in mice and raised prolactin levels. Its antiamphetamine ED50 of 0.3 mg/Kg (4.0 x 10 to the -7 M/Kg) makes it 20x as potent as chlorpromazine with about the same therapeutic index. It is alao active by the oral route. Although the structures of SC-5, 7, 8 and 9 are not yet elucidated, they represent the first instances of neolignans with neuroleptic activity and the first natural products to show such activity since reserpine. Also, unlike all the known neuroleptic drugs, these are not basic and have no nitrogen. They thus present a novel structure to the arena of neuroleptics and can have significant impact on the synthesis, mode of action and clinical use of neuroleptic drugs commonly used in schizophrenia. The objectives of the proposal are to isolate all the active priciples of the plant in quantities sufficient for structure elucidation and evaluation of their neuroleptic potential and provide a structure/activity profile, based on synthesis and/or transformation of the active neolignans. The extracts of the stems and roots will be fractionated based on the toxicity and all the toxic principles will be isolated using chromatographic methods including HPLC. The structures and stereochemistry will be elucidated by a combination of spectral and degradative methods. The active compounds will be tested in a series of behavioral tests in rodents most commonly used for evaluating neuroleptic drugs e.g., antagonism to amphetamine, apomorphine, norepinephrine and tryptamine, as well as selective binding to dopamine receptors. The four natural members and the proposed 'first line' analogues will provide a useful structure/activity profile and synthetic efforts on the active neolignans will be considered after the structural elucidation and evaluation.

Saururus cernuus（一种有毒水杂草）的提取物在分馏中 提供了一系列十种密切相关的化合物（SC-1，SC-2 ...） 似乎属于Neolignans类。 其中SC-5、7、8和9 代表有毒原理，SC-8是主要组成部分。 在 无毒剂量，SC-8在典型的小鼠中显示出行为模式 镇静剂。 在进一步的初步测试中，它抑制了侵略性 反应和苯丙胺引起的刻板印象，并提高催乳素 水平。 它的抗苯丙胺ED50为0.3 mg/kg（4.0 x 10至-7 m/kg） 使其与氯丙嗪具有20倍的效力，并具有大约相同的治疗性 指数。 它在口头路线上是活跃的。 虽然结构 SC-5、7、8和9尚未阐明，它们代表了第一例 具有神经肌肉活性的新木族人，第一个天然产物 显示出这种活动以来，自占治疗。 另外，与所有已知的神经服用不同 药物，这些不是碱性的，没有氮。 他们因此提出了一本小说 神经疗法领域的结构，可以对 神经摄影药的合成，作用方式和临床使用 通常用于精神分裂症。 提案的目标是 隔离植物的所有活性定价，足以 结构阐明和评估其神经肌肉潜力和 根据合成和/或提供结构/活动曲线 活跃的新木兰人的转化。 茎的提取物和 根部将根据毒性和所有毒性分馏 原理将使用包括HPLC在内的色谱方法隔离。 结构和立体化学将通过组合阐明 光谱和降解方法。 活性化合物将在 最常用用于评估的啮齿动物中的一系列行为测试 神经蛋白质药物，例如对苯丙胺的拮抗剂，阿彭胺， 去甲肾上腺素和色胺，以及与多巴胺的选择性结合 受体。 四个自然成员和拟议的“第一线” 类似物将提供有用的结构/活动曲线和合成 在结构之后将考虑对主动新木兰人的努力 阐明和评估。