Department of Anesthesiology, University of Utah, Salt Lake City, Utah, USA.
Curr Opin Anaesthesiol. 2020 Aug;33(4):499-505. doi: 10.1097/ACO.0000000000000879.
The unique demands of modern anesthesia practice require that medications be effective, well tolerated, and efficient. These attributes are increasingly achieved with the soft drug approach, wherein novel active compounds are specifically designed to be susceptible to rapid biotransformation to inactive metabolites. The present review summarizes the historical background and recent trends in soft drug development in anesthesiology.
Soft drug development programs for propranadid, etomidate, and benzodiazepine analogues have been undertaken in recent years. Although all three drugs advanced into human trials, neuro-excitatory adverse effects hampered the propranadid and etomidate analogue projects. Remimazolam, the soft benzodiazepine analogue, is at an advanced stage of development, having already received regulatory approval or review in several countries.
With succinylcholine as the historical forerunner and remifentanil as the modern prototype, the soft drug paradigm continues to hold promise for the future of anesthesia drug development.
现代麻醉实践的独特需求要求药物具有疗效好、耐受性好、效率高的特点。这些特性越来越多地通过软药方法来实现，即在新的活性化合物中特别设计使其易于快速生物转化为无活性的代谢物。本综述总结了麻醉学中软药开发的历史背景和最新趋势。
近年来，已开展了丙泊酚、依托咪酯和苯二氮䓬类类似物的软药开发项目。尽管这三种药物都进入了人体试验，但神经兴奋不良反应阻碍了丙泊酚和依托咪酯类似物项目的进展。瑞马唑仑，软苯二氮䓬类类似物，处于开发的后期阶段，已经在多个国家获得了监管部门的批准或审查。
琥珀酰胆碱作为历史先驱，瑞芬太尼作为现代原型，软药范例继续为未来的麻醉药物开发带来希望。
