Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines.
Inhibition of plasma membrane monoamine transporters by beta-ketoamphetamines.
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DOI：
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发表时间：
1999
影响因子：
5
通讯作者：
N. Cozzi;M. Sievert;A. Shulgin;P. Jacob;A. Ruoho
中科院分区：
文献类型：
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作者：
N. Cozzi;M. Sievert;A. Shulgin;P. Jacob;A. Ruoho
甲卡西酮和甲基酮，甲基苯丙胺和3，4-亚甲二氧基甲基苯丙胺（MDMA）的β-酮类似物，分别进行了体外神经递质摄取抑制试验。β-酮类药物抑制血小板5-羟色胺蓄积的效力比非酮类药物低3倍，IC（50）分别为34.6+/-4.8 microM和5.8+/-0.7 microM。甲卡西酮和甲基酮的效力相似，甲基苯丙胺和MDMA在儿茶酚胺转运单独表达在转染的神经胶质细胞。对于多巴胺摄取，IC（50）分别为0.36+/-0.06 microM和0.82+/-0.17 microM;对于去甲肾上腺素摄取，IC（50）值分别为0.51+/-0.10 microM和1。2+/-0.1 microM。在嗜铬颗粒中，甲卡西酮和甲基酮的5-羟色胺蓄积IC（50）分别为112+/-8.0 microM和166+/-12 microM，分别比甲基苯丙胺和MDMA高10倍。我们的研究结果表明，甲卡西酮和甲基酮有效地抑制质膜儿茶酚胺转运，但只有弱抑制囊泡转运。
Methcathinone and methylone, the beta-ketone analogues of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA), respectively, were tested for neurotransmitter uptake inhibition in vitro. The beta-ketones were threefold less potent than the nonketo drugs at inhibiting platelet serotonin accumulation, with IC(50)'s of 34.6+/-4.8 microM and 5.8+/-0.7 microM, respectively. Methcathinone and methylone were similar in potency to methamphetamine and MDMA at catecholamine transporters individually expressed in transfected glial cells. For dopamine uptake, IC(50)'s were 0.36+/-0.06 microM and 0.82+/-0.17 microM, respectively; for noradrenaline uptake, IC(50) values were 0.51+/-0.10 microM and 1. 2+/-0.1 microM, respectively. In chromaffin granules, IC(50)'s for serotonin accumulation were 112+/-8.0 microM for methcathinone and 166+/-12 microM for methylone, 10-fold higher than the respective values for methamphetamine and MDMA. Our results indicate that methcathinone and methylone potently inhibit plasma membrane catecholamine transporters but only weakly inhibit the vesicle transporter.