Reinforcing effect of pseudoephedrine isomers and the mechanism of action
Reinforcing effect of pseudoephedrine isomers and the mechanism of action
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DOI：
10.1016/j.ejphar.2004.04.030
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发表时间：
2004-06-16
影响因子：
5
通讯作者：
Woolverton, WL
中科院分区：
文献类型：
--
作者：
Wee, S;Ordway, GA;Woolverton, WL
有人提出，麻黄素及其异构体可能会被滥用。当恒河猴（11 = 4）自我给药时，（+）-伪麻黄碱在所有猴子中均发挥正强化剂的作用，（-）-伪麻黄碱在三只猴子中的两只中也发挥了同样的作用。伪麻黄碱异构体的效力比可卡因低10至33倍。在猴脑组织的体外结合中，两种异构体对多巴胺和5-羟色胺转运蛋白的亲和力都较低，至少是可卡因的200倍，但对去甲肾上腺素转运蛋白的亲和力相当。（+）-伪麻黄碱还以相对于可卡因较低的效力阻断293 hDAT细胞中的多巴胺摄取。当给予体内（+）-伪麻黄碱显着取代放射性配体结合多巴胺转运蛋白的效力相当于在自我管理。因此，伪麻黄碱异构体可以起到增强剂的作用，多巴胺转运蛋白的机制可能是这种作用的基础。然而，伪麻黄碱似乎是一种弱麻醉剂，滥用的可能性相对较低。(C)2004 Elsevier B.V.保留所有权利。
It has been proposed that ephedrine and its isomers may have abuse potential. When made available to rhesus monkeys (11 = 4) for self-administration, (+)-pseudoephedrine functioned as a positive reinforcer in all monkeys, as did (-)-pseudoephedrine in two of three monkeys. Pseudoephedrine isomers were 10- to 33-fold less potent than cocaine. In in vitro binding in monkey brain tissue, both isomers had low affinity for dopamine and serotonin transporters by at least 200-fold relative to cocaine, but comparable affinity for norepinephrine transporters. (+)-Pseudoephedrine also blocked dopamine uptake in 293 hDAT cells with low potency relative to cocaine. When given in vivo (+)-pseudoephedrine significantly displaced radioligand binding to dopamine transporters with a potency comparable to that in self-administration. Therefore, pseudoephedrine isomers can function as reinforcers and the mechanism at dopamine transporters may underlie this effect. However, pseudoephedrine appears to be a weak reinforcer and may have relatively low abuse potential. (C) 2004 Elsevier B.V. All rights reserved.