Molecular Containers Bind Drugs of Abuse in Vitro and Reverse the Hyperlocomotive Effect of Methamphetamine in Rats,ChemBioChem

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Molecular Containers Bind Drugs of Abuse in Vitro and Reverse the Hyperlocomotive Effect of Methamphetamine in Rats
ChemBioChem ( IF 2.6 ) Pub Date : 2017-07-12 06:15:50 , DOI: 10.1002/cbic.201700289
Shweta Ganapati ₁ , Stephanie D. Grabitz ₂ , Steven Murkli ₁ , Flora Scheffenbichler ₂ , Maíra I. Rudolph ₂ , Peter Y. Zavalij ₁ , Matthias Eikermann ₂ , Lyle Isaacs ₁

Affiliation

We measured the affinity of five molecular container compounds (calabadions 1 and 2, CB[7], sulfocalix[4]arene, and HP-β-CD) toward seven drugs of abuse in homogenous aqueous solution at physiological pH by various methods (¹H NMR, UV/Vis, isothermal titration calorimetry [ITC]) and found binding constants (K_a values) spanning from <10² to >10⁸ m⁻¹. We also report X-ray crystal structures of CB[7]⋅methamphetamine and 1⋅methamphetamine. We found that 2, but not CB[7], was able to ameliorate the hyperlocomotive activity of rats treated with methamphetamine. The bioavailability of the calabadions and their convergent building block synthesis suggest potential for further structural optimization as reversal agents for intoxication with nonopioid drugs of abuse for which no treatments are currently available.

中文翻译：

分子容器与体外滥用药物结合并逆转甲基苯丙胺对大鼠的超机车作用

我们通过多种方法测量了在生理pH值下均质水溶液中5种分子容器化合物（卡拉巴第1和2，CB [7]，磺胺嘧啶[4]芳烃和HP-β-CD）对7种滥用药物的亲和力（¹ 1 H NMR，UV /可见，等温滴定量热法[ITC]），并发现结合常数（ķ_一个值）从<10跨越²至> 10 ⁸ 米^-1。我们还报告了CB [7] ·甲基苯丙胺和1 ·甲基苯丙胺的X射线晶体结构。我们发现2而不是CB [7]能够改善用甲基苯丙胺治疗的大鼠的超机车活动。aba草的生物利用度及其收敛的构件合成表明，有潜力进一步优化结构，作为可逆滥用非阿片类药物的中毒药物，目前尚无治疗方法。

更新日期：2017-07-13

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