Pharmacology and Metabolism of Salvia divinorum

鼠尾草的药理和代谢

• 批准号: 7407483
• 负责人: DAVID Yue-Wei LEE
• 金额: $ 27.68万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7407483
• 关键词: Biological Assay; Biological Factors; Cactaceae; Development; Drug Addiction; General Population; Health; In Vitro; Lead; Ligands; Liver; Lung; Metabolism; Peyote preparation; Pharmacology; Pharmacotherapy; Plants; RPS19 gene; Risk; Salvia; Smoke; Stramonium; Testing; United States Food and Drug Administration; absorption; analog; in vivo; nervous system disorder; novel; receptor binding; salvinorin A

DESCRIPTION (provided by applicant): A variety of plant-derived psychoactive products such as Salvia divinorum, peyote cactus, and Datura stramonium are readily available to the general public and unregulated by the FDA or DEA. Since these products are natural, much of the public may assume that they are safe. However, the abuse potential and health risks of these psychoactive natural products have not been adequately studied, especially the newly emerged S. divinorum. Thus, there is an urgent need to investigate the active components, their metabolites, and mechanisms of action. S. divinorum is often smoked and absorbed through the lungs. It is conceivable that the initial metabolism of smoked salvinorin A, the major bioactive compound isolated from S. divinorum, takes place in the lung, whereas orally consumed salvinorin A may take place in the liver. The proposed isolation and characterization of new metabolites is to provide much needed information on whether metabolites are active or not, and how these metabolites are stored in and disposed of by the body. The overall objective of this application is to focus on the isolation, extraction, and characterization of bioactive compounds and metabolites of S. divinorum and to understand mechanisms of action through in vitro receptor binding and functional assays and in vivo tests. Our specific aims are 1) to continue our comprehensive isolation and characterization of other potential k-active ligands in S. divinorum; 2) to investigate the active smoke degradation products of S. divinorum; 3) to investigate the absorption, distribution, and metabolism aspects of the identified products; 4) to characterize in vitro and in vivo pharmacological activities of salvinorin A and its analogs and metabolites. A better understanding of k specific natural products isolated from S. divinorum and its metabolites may provide an opportunity for the discovery of novel ligands and the development of potential pharmacotherapies for treating drug addiction and other neurological disorders.

描述（由申请人提供）：各种植物衍生的精神活性产品，如鼠尾草、仙人掌和曼陀罗，公众随时可以获得，并且不受FDA或DEA的监管。由于这些产品是天然的，许多公众可能会认为它们是安全的。然而，这些具有精神活性的天然产品的滥用潜力和健康风险尚未得到充分的研究，特别是新出现的天神花。因此，迫切需要研究其有效成分、代谢产物及其作用机制。通常吸食后通过肺部吸收。可以想象，烟熏salvinorin A的初始代谢是在肺中进行的，而口服salvinorin A可能在肝脏中进行。salvinorin A是从神仙藤中分离出来的主要生物活性化合物。新代谢物的分离和表征是为了提供关于代谢物是否有活性以及这些代谢物如何在体内储存和处置的急需信息。本应用程序的总体目标是集中于分离、提取和表征牡荆的生物活性化合物和代谢物，并通过体外受体结合、功能测定和体内试验了解其作用机制。我们的具体目标是1)继续全面分离和表征其他潜在的k-活性配体；2)研究了香参活性烟雾降解产物；3)调查鉴定产物的吸收、分布和代谢方面的情况；4)表征salvinorin A及其类似物和代谢物的体内外药理活性。更好地了解从葡萄树中分离的k特异性天然产物及其代谢物可能为发现新的配体和开发治疗药物成瘾和其他神经系统疾病的潜在药物疗法提供机会。