Noev Alexey, Morozova Natalia, Suvorov Nikita, Vasil'ev Yuriy, Pankratov Andrei, Grin Mikhail
Department of Chemistry and Technology of Biologically Active Compounds, Medicinal and Organic Chemistry, Institute of Fine Chemical Technologies, MIREA-Russian Technological University, 86 Vernadsky Avenue, 119571 Moscow, Russia.
P. Hertsen Moscow Oncology Research Institute - the Branch of the FSBI "National Medical Research Radiological Centre" of the Ministry of Health of the Russian Federation, 2nd Botkinsky pr. 3, 125284 Moscow, Russia.
Pharmaceuticals (Basel). 2023 Oct 2;16(10):1398. doi: 10.3390/ph16101398.
The toxicity of local anesthetics is a serious problem, given their widespread use. One of the main causes of the side effects of local anesthetics is their non-selectivity of action in the body. A possible way to increase the selectivity of the action of drugs is to use the photopharmacology approach. Previously, we described the light-controlled local anesthetic ethercaine, the biological effect of which can be controlled using light, thereby increasing its selectivity of action. An important limitation of ethercaine was its low solubility in water, limiting the potential of this compound. In this work, we developed a dosage form of ethercaine, which allowed us to increase its solubility from 0.6% to 2% or more. The resulting 1% solution of ethercaine hydrochloride in 4% Kolliphor ELP had high biological activity on the surface anesthesia model, while demonstrating low acute toxicity in mice with intravenous administration (4-5 times less than that of lidocaine).
鉴于局部麻醉药的广泛使用,其毒性是一个严重问题。局部麻醉药产生副作用的主要原因之一是它们在体内作用的非选择性。提高药物作用选择性的一种可能方法是采用光药理学方法。此前,我们描述了光控局部麻醉药依替卡因,其生物学效应可通过光来控制,从而提高其作用选择性。依替卡因的一个重要局限性是其在水中的溶解度低,限制了该化合物的应用潜力。在这项工作中,我们开发了一种依替卡因剂型,使我们能够将其溶解度从0.6%提高到2%或更高。所得的1%盐酸依替卡因在4%聚氧乙烯蓖麻油ELP中的溶液在表面麻醉模型上具有高生物学活性,同时在小鼠静脉给药时显示出低急性毒性(比利多卡因低4至5倍)。