立体异构体的钙拮抗剂的明显区别在于其效能作为钙阻断剂在调节药物运输22也同样有效。

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Hollt V, Kouba M, Dietel M,沃格特G

立体异构体的钙拮抗剂的明显区别在于其效能作为钙阻断剂在调节药物运输22也同样有效。

生物化学杂志。1992年6月23日,43 (12):2601 - 8。0006 - 2952 . doi: 10.1016 / (92) 90149 - d。

PubMed ID

1352973 (在PubMed

]

文摘

维拉帕米的(-)异构体是10倍更有效钙拮抗剂(+)异构体。然而,两种对映体都同样有效增加细胞积累抗癌药物(格鲁伯et al ., Int J癌症41:224 - 226,1988]。除了维拉帕米,存在各种各样的立体异构体和phenylalkylamines dihydropyridine结构明显的效力不同钙拮抗剂。我们已经测试了这些药物的能力增加细胞内积累[3 h]长春花碱([3 h]轮式侦察车)doxorubicin-resistant细胞系(F4-6RADR)来源于朋友小鼠白血病细胞系(F4-6P)和COS-7猴肾细胞。两种类型的细胞表达大量的多药耐药性基因1 mRNA和22所揭示的RNA和免疫污点分析。的对映体phenylalkylamine结构(维拉帕米(+ / -);(+ / -)-devapamil;(+ / -)-emopamil)]和[dihydropyridine结构(+ / -)-isradipine;(+ / -)-nimodipine;(+ / -)非洛地平; (+/-)-nitrendipine; (+/-)-niguldipine] increased [3H]VBL accumulation in both cell lines at micromolar concentrations. Although the stereoisomers of these drugs differ markedly in their potency as calcium channel blockers they were about equally effective in increasing VBL levels in the cells. There was no substantial difference in the potencies of the phenylalkylamine drugs in affecting cellular [3H]VBL transport. Major potency differences, however, were observed in the dihydropyridine drug series with the niguldipine isomers as the most effective drugs. Moreover, the niguldipine enantiomers were equally as effective in reversing VBL resistance in F4-6RADR cells as were the verapamil enantiomers. Since (-)-niguldipine (B859-35) displays a 45-fold lower affinity for calcium channel binding sites than (+)-niguldipine, but is equally potent in inhibiting drug transport by P-glycoprotein and in reversing drug resistance, it may be, in addition to (+)-verapamil, another useful candidate drug for the treatment of multidrug resistance in cancer patients.

DrugBank数据引用了这篇文章

药物转运蛋白

药物	转运体	类	生物	药理作用	行动
Niguldipine	22 - 1	蛋白质	人类	未知的	抑制剂	细节