Potential of Ligands for Trace Amine-Associated Receptor 1 (TAAR1) in the Management of Substance Use Disorders.
Potential of Ligands for Trace Amine-Associated Receptor 1 (TAAR1) in the Management of Substance Use Disorders.
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DOI：
10.1007/s40263-021-00871-4
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发表时间：
2021-12
期刊：
影响因子：
6
通讯作者：
Li JX
中科院分区：
文献类型：
--
作者：
Wu R;Li JX
微量胺，包括β-苯乙胺（β-PEA）、对酪胺（TYR）、色胺（TRP）和对章鱼胺（OCT），是一类在哺乳动物大脑中表达水平较低的胺类。由于其与传统单胺类化合物结构相似，微量胺类化合物与单胺能系统之间的联系早已确立。微量胺相关受体1 （Trace amine associated receptor 1, TAAR1）是TAARs家族中最具特征的受体，已被证实可被TYR和PEA等微量胺激活。同时，儿茶酚胺代谢物和安非他明类似物也是TAAR1的有效激动剂，暗示其在介导单胺能系统和物质使用障碍中的作用。在中枢神经系统中，TAAR1在涉及多巴胺能、血清素能和谷氨酸能传递的脑区表达。遗传动物模型和电生理研究表明，TAAR1是单胺能系统的有效调节剂，TAAR1激动剂可能是治疗物质使用障碍的潜在药物疗法。选择性和有效的工程TAAR1配体，包括全受体（RO5166017和RO5256390）和部分受体（RO5203648， RO5263397和RO5073012）激动剂和拮抗剂EPPTB (N-（3-乙氧基苯基）-4-（1-吡咯烷基）-3-（三氟甲基）苯酰胺，RO5212773)，是研究TAAR1功能的宝贵工具，在开发基于TAAR1的药物疗法治疗物质使用障碍方面具有很高的潜力。尽管已经取得了一些进展，但为了测试TAAR1配体在治疗精神疾病，特别是物质使用障碍方面的潜力和功效，还需要进行更多的临床研究。
Trace amines, including β-phenylethylamine (β-PEA), p-tyramine (TYR), tryptamine (TRP) and p-octopamine (OCT), represent a group of amines expressed at low levels in the mammalian brain. Given the close structural similarities to traditional monoamines, the links between trace amines and the monoaminergic system have long been established. Trace amine associated receptor 1 (TAAR1), the most well characterized receptor in the TAARs family, has been shown to be potently activated by trace amines like TYR and PEA. Meanwhile, catecholamine metabolites and amphetamine analogs are also potent agonists of TAAR1, implicating its role in mediating the monoaminergic system and substance use disorders. In the central nervous system, TAAR1 is expressed in brain regions involved in dopaminergic, serotonergic and glutamatergic transmission. Genetic animal models and electrophysiological studies have revealed that TAAR1 is a potent modulator of the monoaminergic system, and TAAR1 agonists may be potential pharmacotherapies for the treatment of substance use disorders. Selective and potent engineered TAAR1 ligands, including full (RO5166017 and RO5256390) and partial (RO5203648, RO5263397 and RO5073012) agonists and the antagonist EPPTB (N-(3-ethoxyphenyl)-4-(1-pyrrolidinyl)-3-(trifluoromethyl)benzamide, RO5212773), serve as invaluable tools for the investigation of TAAR1 functions and display high potential for the development of TAAR1-based pharmacotherapies for the treatment of substance use disorders. Despite a number of advances that have been made, more clinical studies are warranted in order to test the potential and efficacy of TAAR1 ligands in the treatment of psychiatric disorders, especially substance use disorders.
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安非他明、3,4-亚甲二氧基甲基苯丙胺、麦角酸二乙酰胺和儿茶酚胺神经递质的代谢物是大鼠微量胺受体的激动剂
影响因子：
3.6
作者：
Bunzow, JR;Sonders, MS;Grandy, DK
通讯作者：
Grandy, DK
影响因子：
6.1
作者：
BORISON, RL;MOSNAIM, AD;SABELLI, HC
通讯作者：
SABELLI, HC
DOI：
10.1093/ijnp/pyy071
发表时间：
2018-10-01
期刊：
The international journal of neuropsychopharmacology
影响因子：
--
作者：
Berg KA;Clarke WP
通讯作者：
Clarke WP
影响因子：
4.6
作者：
Asif-Malik A;Hoener MC;Canales JJ
通讯作者：
Canales JJ
影响因子：
7.6
作者：
Espinoza, Stefano;Lignani, Gabriele;Gainetdinov, Raul R.
通讯作者：
Gainetdinov, Raul R.