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-Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation, 2nd Botkinsky pr. 3, 125284 Moscow, Russia.
Int J Mol Sci. 2022 May 11;23(10):5352. doi: 10.3390/ijms23105352.
Pain is a common symptom that impairs the quality of life for people around the world. Local anesthetics widely used for pain relief have a number of side effects, which makes the development of both new drugs and new ways to control their activity particularly important. Photopharmacology makes it possible to reduce the side effects of an anesthetic and control its biological activity in the body. The purpose of this work was to create a new light-controlled local anesthetic and study its biological activity in animals. A compound with a simple scheme of synthesis was chosen to shift the UV-Vis absorption band towards the visible range of the spectrum and was synthesized for the first time. Some computer calculations were performed to make sure that the aforementioned changes would not lead to loss of biological activity. The micellar form of the new compound was prepared, and in vivo biological studies were carried out in rabbits. The existence of a local anesthetic effect, which disappeared almost completely on irradiation with light (λ = 395 nm), was shown using the surface anesthesia model. Moreover, the possibility of multiple reversible changes in the biological activity of ethercaine under the action of light was demonstrated. The latter compound manifests no local irritating effect, either. The data obtained indicate the prospects for the development of new compounds based on azobenzene for light-controlled local anesthesia.
疼痛是一种常见的症状，会降低全球人民的生活质量。广泛用于缓解疼痛的局部麻醉剂有许多副作用，这使得开发新药物和控制其活性的新方法变得尤为重要。光药理学使得减少麻醉剂的副作用并控制其在体内的生物活性成为可能。本工作的目的是创建一种新的光控局部麻醉剂并研究其在动物中的生物活性。选择了一种具有简单合成方案的化合物，以将 UV-Vis 吸收带移至光谱的可见范围，并首次合成了该化合物。进行了一些计算机计算以确保上述变化不会导致生物活性丧失。制备了新化合物的胶束形式，并在兔子体内进行了生物研究。使用表面麻醉模型显示出存在局部麻醉效果，该效果在光照射（λ=395nm）下几乎完全消失。此外，还证明了醚卡因的生物活性在光作用下可以多次可逆变化。后者化合物也没有局部刺激性作用。所得数据表明，基于偶氮苯的新型化合物在光控局部麻醉方面具有广阔的发展前景。
