Reinforcing and discriminative-stimulus effects of ephedrine isomers in rhesus monkeys
Reinforcing and discriminative-stimulus effects of ephedrine isomers in rhesus monkeys
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DOI：
10.1016/s0376-8716(01)00143-0
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发表时间：
2001-12-01
影响因子：
4.2
通讯作者：
Woolverton, WL
中科院分区：
文献类型：
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作者：
Anderson, KG;Winger, G;Woolverton, WL
麻黄素是一种拟交感神经药物，目前在许多非处方药中都有发现。这种化合物以四种异构体的形式存在。除了外消旋混合物外，还评估了它们的积极增强作用以及它们作为歧视性刺激与(+)-苯丙胺的相似性。3只恒河猴(N=3)静脉注射可卡因(0.1 mg/kg/inj)或注射生理盐水作为杠杆压迫的结果，在试验过程中，当每种药物/剂量替代可卡因或生理盐水时，除(-)-伪麻黄碱外，所有麻黄素化合物(测试范围：0.03-3.0 mg/kg/inj)均可自行给药。然而，由于溶解度的限制，(-)-伪麻黄碱异构体在有限的剂量范围内进行了评估。系统地增加注射所需的反应次数表明，这些异构体不如可卡因那样有效。将经训练的恒河猴(N=3)区分灌胃1.0 mg/kg(+)苯丙胺和生理盐水，用麻黄碱异构体和外消旋混合物进行替代试验。当灌胃给药时，在至少一名受试者中，至少一剂所有麻黄碱异构体取代(+)-苯丙胺辨别性刺激。然而，(+)-苯丙胺样效应与剂量没有系统的相关性，当比较(-)-麻黄碱和(+)-苯丙胺在三种不同给药途径的辨别刺激效应时，肌肉和静脉给药均可观察到完全的、剂量相关的、(+)-苯丙胺样反应。综上所述，这些结果表明麻黄素具有类似精神运动兴奋剂的滥用潜力，低于可卡因。肠外给药可能会增强精神运动兴奋剂的作用。(C)2001爱思唯尔爱尔兰科学有限公司。保留所有权利。
Ephedrine is a sympathomimetic drug that is currently found in many over-the-counter preparations. This compound exists as four isomers which. in addition to a racemic mixture, were evaluated for their positive reinforcing effects and for their similarity to (+)-amphetamine as a discriminative stimulus. Rhesus monkeys (N=3) with intravenous cocaine (0.1 mg/kg/inj) or saline as a consequence for lever pressing were shown to self-administer all of the ephedrine compounds (range tested: 0.03-3.0 mg/kg/inj), with the exception of (-)-pseudoephedrine, when each drug/dose was substituted for cocaine or saline during test sessions. However, the (-)-pseudoephedrine isomer was evaluated within a limited dose range due to solubility limitations. Systematically increasing the number of responses required for an injection indicated that these isomers were not as effective as reinforcers as was cocaine. Rhesus monkeys (N=3) trained to discriminate intragastric 1.0 mg/kg (+)-amphetamine from saline were given substitution tests with the ephedrine isomers and the racemic mixture. When given intragastrically, at least one dose of all the ephedrine isomers substituted for the (+)-amphetamine discriminative stimulus in at least one of the subjects tested. However, (+)-amphetamine-like effects were not systematically related to dose, When the discriminative-stimulus effects of (-)-ephedrine were also compared with those of (+)-amphetamine across three different routes of administration, full, dose-related, (+)-amphetamine-like responding was observed with both the intramuscular and intravenous routes. Taken together, these results suggest that the ephedrines have psychomotor stimulant-like abuse potential, lower than that of cocaine. Parenteral administration may enhance psychomotor-stimulant-like effects. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.