EXTRACT OF SAURURUS WITH NEUROLEPTIC ACTIVITY

三白草(有毒水生杂草)分级提取液的研究 给出了一系列十个密切相关的化合物(SC-1，SC-2…)哪一个 似乎属于新木脂素类。其中，SC-5、7、8和9 代表有毒原则，SC-8是主要成分。在… 无毒剂量，SC-8在小鼠身上显示出典型的主要 镇静剂。在进一步的初步测试中，它抑制了攻击性 反应和苯丙胺诱导的小鼠刻板行为及催乳素升高 级别。其抗安非他明ED50为0.3毫克/公斤(4.0×10至-7M/公斤) 使其效力是氯丙嗪的20倍，而治疗效果几乎相同 指数。它是通过口服途径活跃的。尽管它的结构 SC-5、7、8和9尚未阐明，它们是第一个实例 具有神经镇静剂活性的新木脂素和第一批 显示出利血平以来的这种活性。此外，与所有已知的神经镇静剂不同 药物，这些都不是基本的，也不含氮。因此，他们推出了一部小说 结构延伸到抗精神病药的领域，并可能对 抗精神病药物的合成、作用方式及临床应用 常用于精神分裂症。该提案的目标是 分离出植物的所有活性成分，数量足以 它们的结构鉴定和抗神经药活性的评价 基于合成和/或提供结构/活动简档 活性新木脂素的转化。茎和茎的提取液 根将根据毒性和所有有毒的 主要成分将使用包括高效液相色谱法在内的层析方法进行分离。 结构和立体化学将通过以下组合来阐明 光谱和降解法。这些活性化合物将在 对啮齿动物进行的一系列行为测试，最常用于评估 抗精神病药物，如对苯丙胺、阿朴吗啡的拮抗作用， 去甲肾上腺素和色胺，以及与多巴胺的选择性结合 感受器。四个自然成员和提出的“第一条线” 类似物将提供有用的结构/活性分布和合成 在结构调整后，将考虑对活性新木脂素的努力 说明和评价。

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.