Sohajda Tamás, Fábián Ákos, Tuza Kata, Malanga Milo, Benkovics Gábor, Fülesdi Béla, Tassonyi Edömér, Szente Lajos
Cyclolab Cyclodextrin Research and Development Laboratory Ltd., H-1097, Illatos út 7, Budapest, Hungary.
University of Debrecen, Department of Anesthesiology and Intensive Care, H-4032, Nagyerdei krt. 98, Debrecen, Hungary.
Int J Pharm. 2017 Oct 15;531(2):512-520. doi: 10.1016/j.ijpharm.2017.03.060. Epub 2017 Mar 31.
Applying patient friendly and cost-efficient medications in healthcare will be a real challenge in the 21st century. Sugammadex is a selective, yet expensive agent used for the post-surgical reversal of neuromuscular block since 2008. A wide library of cyclodextrin-based follow-ups, having potentially similar affinity towards target aminosteroid type neuromuscular blocking agents has been established. Almost 20 compounds were assessed with respect to in vitro affinity against three commonly applied drugs. Based on the capillary electrophoretic screening, carboxymethylated and sulfobutylated gamma-cyclodextrin derivatives have the potential to be promising lead molecules for their affinity towards pipecuronium was identical or even superior to Sugammadex. Carboxymethylated gamma-cyclodextrin showed efficient and complete reversal of the pipecuronium induced neuromuscular block in an ex vivo rat diaphragm experiment.
在医疗保健中应用对患者友好且成本效益高的药物将是21世纪的一项真正挑战。自2008年以来，舒更葡糖钠是一种用于术后逆转神经肌肉阻滞的选择性但昂贵的药物。已经建立了一个基于环糊精的后续化合物库，这些化合物对目标氨基甾体类神经肌肉阻滞剂具有潜在的相似亲和力。针对三种常用药物的体外亲和力评估了近20种化合物。基于毛细管电泳筛选，羧甲基化和磺丁基化的γ-环糊精衍生物因其对哌库溴铵的亲和力与舒更葡糖钠相同甚至更高，而有潜力成为有前景的先导分子。在离体大鼠膈肌实验中，羧甲基化γ-环糊精显示出对哌库溴铵诱导的神经肌肉阻滞有有效且完全的逆转作用。
