Fleckenstein A E, Kopajtic T A, Boja J W, Carroll F I, Kuhar M J
National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Eur J Pharmacol. 1996 Sep 12;311(2-3):109-14. doi: 10.1016/0014-2999(96)00423-2.
Three cocaine analogs were compared with cocaine for the capacity to affect: (1) dopamine transporter binding and function; and (2) locomotor activity. RTI-55 (3 beta-[4-iodophenyl]tropane-2 beta-carboxylic acid methyl ester tartrate), RTI-121 (3 beta-[4-iodophenyl] tropan-2 beta-carboxylic acid isopropyl ester hydrochloride) and RTI-130 (3 beta-[4-chlorophenyl-2 beta-[1,2,4-oxadiazol-3-phenyl-5-yl]tropane hydrochloride) competed for [3H]WIN 35428 binding in rat striatum in vitro, with IC50 values at least 50-fold less than that of cocaine. These analogs inhibited [3H]dopamine transport into rat striatal synaptosomes, with IC50 values again less (at least 100-fold) than that for cocaine. Intravenous RTI-55, RTI-121 or RTI-130 injection effected dose-related increases in locomotor activity in mice, with estimated relative potencies at least 10-fold greater than that of cocaine. These increases were long lasting: whereas increased activity ceased within 2 h after cocaine administration, increased locomotion was observed at least 10 h after RTI-55, RTI-121, or RTI-130 administration. Parallel line analysis indicated that the slopes of the ascending portion of the RTI-121 and RTI-130 dose-response curves differed from that of cocaine, suggesting the involvement of mechanisms different from that of cocaine.
（1）多巴胺转运体结合及功能；（2）运动活性。RTI-55（3β-[4-碘苯基]托烷-2β-羧酸甲酯酒石酸盐）、RTI-121（3β-[4-碘苯基]托烷-2β-羧酸异丙酯盐酸盐）和RTI-130（3β-[4-氯苯基-2β-[1,2,4-恶二唑-3-苯基-5-基]托烷盐酸盐）在体外对大鼠纹状体中[3H]WIN 35428结合具有竞争作用，其半数抑制浓度（IC50）值比可卡因至少低50倍。这些类似物抑制[3H]多巴胺转运至大鼠纹状体突触体，IC50值同样比可卡因低（至少100倍）。静脉注射RTI-55、RTI-121或RTI-130可使小鼠运动活性呈剂量相关增加，估计相对效力比可卡因至少高10倍。这些增加作用持久：可卡因给药后2小时内活动增加停止，而RTI-55、RTI-121或RTI-130给药后至少10小时仍可观察到运动增加。平行线分析表明，RTI-121和RTI-130剂量-反应曲线上升部分的斜率与可卡因不同，提示涉及与可卡因不同的机制。
