Pharmacology and Metabolism of Salvia divinorum

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，仙人掌和曼陀罗是容易获得的一般公众和不受FDA或DEA的监管。由于这些产品是天然的，许多公众可能认为它们是安全的。然而，这些精神活性天然产物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S。神圣的因此，迫切需要研究其活性成分、代谢产物及其作用机制。S. Divinorum通常被烟熏并通过肺部吸收。可以想象，从S.例如，口服鼠尾草素A可在肺中发生，而口服鼠尾草素A可在肝中发生。提出的新代谢物的分离和表征是为了提供关于代谢物是否具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。本申请的总体目标是集中于S.通过体外受体结合和功能测定以及体内试验，了解divinorum的作用机制。我们的具体目标是：1）继续全面分离和表征S.（2）研究S. divinorum; 3）研究所鉴定产物的吸收、分布和代谢方面; 4）表征鼠尾草素A及其类似物和代谢物的体外和体内药理学活性。进一步了解从S. divinorum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了机会。

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.