Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders.
Salvinorin A, a kappa-opioid receptor agonist hallucinogen: pharmacology and potential template for novel pharmacotherapeutic agents in neuropsychiatric disorders.
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DOI：
10.3389/fphar.2015.00190
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发表时间：
2015
影响因子：
5.6
通讯作者：
Kreek MJ
中科院分区：
文献类型：
--
作者：
Butelman ER;Kreek MJ
丹参甲素是一种有效的致幻剂，从民族药用植物丹参中分离出来。Salvinorin A是一种选择性高效的kappa-阿片受体(KOPr)激动剂，因此与KOPr系统及其内源性激动剂配体(强啡肽)具有更高的功能，包括认知和知觉效应。Salvinorin A是唯一在研究或医疗机构之外广泛可获得的选择性KOPr配体，含有Salvinorin A的产品已被频繁地用于非医疗用途。众所周知，大脑中的KOPr/强啡肽系统是对多巴胺能功能的强大反调节机制，多巴胺能功能在情绪和由天然和化学增强剂(包括滥用药物)产生的奖励中非常重要。因此，在临床前模型中，KOPr的激活(包括Salvinorin A)可以导致厌恶和快感缺失。Salvinorin A也是一种全新的药物化学方法支架，因为与其他已知的阿片类配体不同，它是一种无氮的新十字烷。正在进行的努力的目标是发现具有潜在KOPr介导的药物治疗作用(包括部分激动剂或偏向激动剂作用)的新的半合成丹参素类似物，减少与丹参素A相关的不良影响的负担。
Salvinorin A is a potent hallucinogen, isolated from the ethnomedical plant Salvia divinorum. Salvinorin A is a selective high efficacy kappa-opioid receptor (KOPr) agonist, and thus implicates the KOPr system and its endogenous agonist ligands (the dynorphins) in higher functions, including cognition and perceptual effects. Salvinorin A is the only selective KOPr ligand to be widely available outside research or medical settings, and salvinorin A-containing products have undergone frequent non-medical use. KOPr/dynorphin systems in the brain are known to be powerful counter-modulatory mechanisms to dopaminergic function, which is important in mood and reward engendered by natural and chemical reinforcers (including drugs of abuse). KOPr activation (including by salvinorin A) can thus cause aversion and anhedonia in preclinical models. Salvinorin A is also a completely new scaffold for medicinal chemistry approaches, since it is a non-nitrogenous neoclerodane, unlike other known opioid ligands. Ongoing efforts have the goal of discovering novel semi-synthetic salvinorin analogs with potential KOPr-mediated pharmacotherapeutic effects (including partial agonist or biased agonist effects), with a reduced burden of undesirable effects associated with salvinorin A.