Ether business: scientists have created a fundamentally new anesthetic with light activation

Russian scientists have created a new anesthetic that is activated by light. Existing topical medications are toxic, which limits their use in children under four years of age, as well as in adult patients with certain diseases. The new drug blocks pain channels without such a load. As the experts interviewed by Izvestia noted, the technology is at the forefront of science, and such a drug will be especially in demand in microsurgery, dentistry, and long-term oncological procedures. However, the research team is still at the beginning of the journey.

Anesthetic with light activation

A team of scientists from the Department of Operative Surgery and Topographic Anatomy at Sechenov University and RTU MIREA has developed a fundamentally new anesthetic. Due to its unique properties, experts plan to use it, including for age-related patients who suffer from chronic pain caused by malignant neoplasms.

As the developers explained, today in the arsenal of doctors there is a fairly large number of local painkillers for administration. They can either partially interrupt the pain or turn it off completely. All of them were synthesized in the second half of the twentieth century.

— At that time, synthesis was accompanied by giving them the property of toxicity. Accordingly, this limits their use in children under four years of age, as well as in adult patients with certain diseases. Toxic drugs do not have the necessary effect in oncological pain and the inflammatory process," Yuri Vasiliev, professor of the Department of Operative Surgery and Topographic Anatomy at Sechenov University, told Izvestia.

The depth of penetration of anesthetics is quite large, but the doctor inserts the needle virtually "blindly", assuming that the individual anatomy will smooth out some inaccuracies. Nevertheless, in maxillofacial surgery, the effectiveness of local anesthesia for pain relief of the third branch of the trigeminal nerve is still insufficient, the doctors noted. Thus, the multidisciplinary development team faced the question of finding an incentive that would give the drugs new properties or change them.

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This is how the idea of a local painkiller that will be activated by light appeared.

— As a result of cellular testing and research on laboratory animals, a new molecule has been developed — "etherocoin", from the Latin word "ether". There are activators at the two ends of the molecule of this substance. So, if an anesthetic is injected into the tissue, but its effect is insufficient, then a special long—wave light must be directed at the area of its administration, and the activators begin to unfold into cis and transposition. That is, the reversal of the "tail" of the molecule blocks the channels that are responsible for the transmission of pain — this ensures complete anesthesia," explained Yuri Vasiliev.

At the end of the operation, when it is necessary to check whether the sensitivity of the patient has returned, you need to shine the light again, and then the molecule unfolds once more. Studies on laboratory animals have shown that a one percent solution of "etherocoin" is suitable for both application and infiltration anesthesia.

Properties of the new anesthetic

Light-controlled drugs have not only analgesic, but also antiarrhythmic properties, Mikhail Green, Head of the Department of Chemistry and Technology of Biologically Active Compounds, Medical and Organic Chemistry at RTU MIREA, told Izvestia.

— Traditional methods of treating arrhythmias can leave scars on the heart, which in itself can provoke new rhythm disturbances. Light-controlled antiarrhythmics allow you to "reset" problem areas of the heart and restore their normal functioning without negative consequences. We can temporarily deactivate problem areas and then restore their function," he stressed.

The creation of photo-switchable drugs, such as the developed etherocoin, represents an important technological breakthrough in modern pharmacology. Unlike existing anesthetics, whose effect is limited by concentration and time, the use of light as an "external switch" opens up completely new possibilities for precise control of the depth and duration of anesthesia in real time, the head of the Personalized Medicine Center of Excellence at Kazan (Volga Region) Federal University, corresponding member of the Academy of Sciences, told Izvestia. Albert Rizvanov of the Republic of Tatarstan.

— This is especially in demand in microsurgery, dentistry and during long-term oncological procedures. At the same time, it is obvious that the work is still at an early conceptual stage. The problem of the limited penetration depth of the light used (near ultraviolet and visible range) has to be solved, which makes it difficult to apply the approach to deeply located nerves and internal organs. It will also be necessary to significantly increase the photostability and biocompatibility of such compounds and minimize the toxicity of their decomposition products," he noted.

The problem of pain and pain relief has always faced the global medical community, along with improving the quality of life. Today, there are many anesthetics, but world scientists continue their research on the "ideal anesthetic" that would meet such requirements as safety, accessibility, minimal side effects, and ease of use, said NTI Helsnet market expert, head of the Intensive care Unit and Intensive Care Unit of the SamSMU Clinics of the Russian Ministry of Health, an anesthesiologist and intensive care specialist. Alexandra Lunina.

— The most acute issue is in elderly patients who have a bunch of concomitant diseases: sometimes general anesthetics have side effects, and sometimes they are contraindicated. The practitioner faces a difficult choice of anti-pain medication. Therefore, it is gratifying that our Russian specialists were able to develop a local anesthetic with an antiarrhythmic effect. And we know that the first place in the list of mortality is occupied by diseases of the cardiovascular system. Many diseases are "getting younger," a large number of patients with rhythm disorders and complex rhythm disorders, and it is very important to have pain medications with antiarrhythmic effects, she said.

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The authors' works are particularly interesting because they demonstrate controlled switching directly in living organisms, said Ekaterina Skorb, Director of the ITMO Scientific and Educational Center for Infochemistry.

— Vivid examples of how the 2022 Nobel Prize in Chemistry for "click chemistry and bioorthogonal reactions" confirmed the importance of controlled chemical processes in vivo (in living organisms) - like the work of Sharpless and Bertozzi (2022 laureates), the authors of this article show how it is possible to change the properties of biologically active molecules in real time.- she noted.

Currently, the team of scientists is working on reducing the systemic toxicity of the drug and a new delivery system. The main goal of the team is to start clinical use of the drug primarily in elderly people with chronic pain and oncological pain.