A Novel Photoswitchable Azobenzene-Containing Local Anesthetic Ethercaine with Light-Controlled Biological Activity In Vivo

Abstract

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.

Keywords

• ethercaine
• fotocaine
• photopharmacology
• photoswitchable local anesthetic
• azobenzene
• micelles