Department of Anesthesiology, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3740-5. doi: 10.1073/pnas.0911542107. Epub 2010 Feb 4.
Sensory-selective local anesthesia has long been a key goal in local anesthetic development. For example, it allows women to be pain-free during labor without compromising their ability to push. Here we show that prolonged sensory-selective nerve block can be produced by specific concentrations of surfactants-such as are used to enhance drug flux across skin-in combination with QX-314, a lidocaine derivative that has relative difficulty penetrating nerves. For example, injection of 25 mM QX-314 in 30 mM octyltrimethylammonium bromide (OTAB) lasted up to 7 h. Sensory selectivity was imparted to varying degrees by cationic, neutral, and anionic surfactants, and also was achieved with another lidocaine derivative, QX-222. Simultaneous injection of OTAB at a s.c. injection site remote from the sciatic nerve did not result in prolonged sensory-specific nerve blockade from QX-314, suggesting that the observed effect is due to a local interaction between the surfactant and the lidocaine derivative, not a systemic effect.
感觉选择性局部麻醉一直是局部麻醉剂开发的一个关键目标。例如,它可以让女性在分娩时无痛,而不会影响她们的分娩能力。在这里,我们表明,通过特定浓度的表面活性剂(如用于增强药物跨皮通量的表面活性剂)与 QX-314(一种相对难以穿透神经的利多卡因衍生物)结合,可以产生长时间的感觉选择性神经阻滞。例如,注射 25mM 的 QX-314 在 30mM 的辛基三甲基溴化铵(OTAB)中可以持续长达 7 小时。阳离子、中性和阴离子表面活性剂赋予感觉选择性的程度不同,另一种利多卡因衍生物 QX-222 也能实现感觉选择性。同时在远离坐骨神经的皮下注射部位注射 OTAB,不会导致 QX-314 产生长时间的感觉特异性神经阻滞,这表明观察到的效果是由于表面活性剂和利多卡因衍生物之间的局部相互作用,而不是全身作用。