Witkin J M, Savtchenko N, Mashkovsky M, Beekman M, Munzar P, Gasior M, Goldberg S R, Ungard J T, Kim J, Shippenberg T, Chefer V
Drug Development Group and Integrative Neuroscience Unit Addiction Research Center, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.
J Pharmacol Exp Ther. 1999 Mar;288(3):1298-310.
Sydnocarb (3-(beta-phenylisopropyl)-N-phenylcarbamoylsydnonimine) is a psychostimulant in clinical practice in Russia as a primary and adjunct therapy for a host of psychiatric disorders, including schizophrenia and depression. It has been described as a stimulant with an addiction liability and toxicity less than that of amphetamines. The present study undertook to evaluate the psychomotor stimulant effects of sydnocarb in comparison to those of methamphetamine. Sydnocarb increased locomotor activity of mice with reduced potency (approximately 10-fold) and efficacy compared with methamphetamine. Sydnocarb blocked the locomotor depressant effects of haloperidol at doses that were inactive when given alone. The locomotor stimulant effects of both methamphetamine and sydnocarb were dose-dependently blocked by the dopamine D1 and D2 antagonists SCH 39166 and spiperone, respectively; blockade generally occurred at doses of the antagonists that did not depress locomotor activity when given alone. In mice trained to discriminate methamphetamine from saline, sydnocarb fully substituted for methamphetamine with a 9-fold lower potency. When substituted for methamphetamine under self-administration experiments in rats, 10-fold higher concentrations of sydnocarb maintained responding by its i.v. presentation. Sydnocarb engendered stereotypy in high doses with approximately a 2-fold lower potency than methamphetamine. However, sydnocarb was much less efficacious than methamphetamine in inducing stereotyped behavior. Both sydnocarb and methamphetamine increased dialysate levels of dopamine in mouse striatum; however, the potency and efficacy of sydnocarb was less than methamphetamine. The convulsive effects of cocaine were significantly enhanced by the coadministration of nontoxic doses of methamphetamine but not of sydnocarb. Taken together, the present findings indicate that sydnocarb has psychomotor stimulant effects that are shared by methamphetamine while demonstrating a reduced behavioral toxicity.
喜得镇（3-（β-苯异丙基）-N-苯基氨基甲酰基西地那明）在俄罗斯是一种精神振奋剂，在临床实践中作为多种精神疾病（包括精神分裂症和抑郁症）的主要及辅助治疗药物。它被描述为一种成瘾性和毒性低于苯丙胺类药物的兴奋剂。本研究旨在评估喜得镇与甲基苯丙胺相比的精神运动兴奋作用。与甲基苯丙胺相比，喜得镇增强小鼠自发活动的效力（约低10倍）和效能降低。喜得镇能阻断氟哌啶醇对自发活动的抑制作用，而其单独给药时无活性剂量即可发挥此作用。甲基苯丙胺和喜得镇的精神运动兴奋作用分别被多巴胺D1和D2拮抗剂SCH 39166和螺哌隆剂量依赖性地阻断；阻断作用通常发生在拮抗剂单独给药时不抑制自发活动的剂量。在训练用于区分甲基苯丙胺和生理盐水的小鼠中，喜得镇能完全替代甲基苯丙胺，但效力低9倍。在大鼠的自我给药实验中，当替代甲基苯丙胺时，喜得镇静脉给药维持反应所需的浓度高10倍。高剂量的喜得镇会产生刻板行为，其效力比甲基苯丙胺低约2倍。然而，喜得镇诱导刻板行为的效能远低于甲基苯丙胺。喜得镇和甲基苯丙胺均可增加小鼠纹状体透析液中多巴胺的水平；然而，喜得镇的效力和效能均低于甲基苯丙胺。无毒剂量的甲基苯丙胺但不是喜得镇共同给药可显著增强可卡因的惊厥作用。综上所述，目前的研究结果表明，喜得镇具有与甲基苯丙胺共同的精神运动兴奋作用，同时表现出较低的行为毒性。
