Azobenzene-Based Voltage-Gated Sodium Channel Blockers with Light-Controlled Local Anesthetic and Antiarrhythmic Activity

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Abstract

The work is devoted to the synthesis of new light-controlled voltage-gated sodium (Nav) channel blockers based on azobenzene and the study of their local anesthetic and antiarrhythmic properties. The effect of ethercaine and two of its new derivatives on native Nav channels was studied in vitro using the patch-clamp method on isolated excitable cells (neurons and cardiomyocytes) of a rat, and local anesthetic activity of the compounds was evaluated on rabbit’s eye cornea. Studies of the effect of the obtained compounds on the conductivity of excitation waves in cardiomyocyte cultures using the optical mapping method were performed. The effective light-dependent biological activity of ethercaine and its derivatives allows us to consider the resulting compounds as potential tools for light-controlled local anesthesia, as well as for non-invasive ablation of arrhythmia in the heart in cardiology.

About the authors

A. N Noev

MIREA – Russian Technological University; P. Hertsen Moscow Oncology Research Institute – Branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: aleksej-noev@yandex.ru
Moscow, Russia; Moscow, Russia

S. G Kovalenko

Moscow Institute of Physics and Technology (National Research University); M.F. Vladimirsky Moscow Region Research Clinical Institute

Dolgoprudny, Russia; Moscow, Russia

E. D Gataulina

I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

St. Petersburg, Russia

E. A Turchaninova

Moscow Institute of Physics and Technology (National Research University)

Dolgoprudny, Russia

V. D Dzhabrailov

Moscow Institute of Physics and Technology (National Research University)

Dolgoprudny, Russia

A. A Aitova

Moscow Institute of Physics and Technology (National Research University),

Dolgoprudny, Russia

D. A Likhobabina

MIREA – Russian Technological University

Moscow, Russia

J. A Sutemieva

MIREA – Russian Technological University

Moscow, Russia

S. R Frolova

Moscow Institute of Physics and Technology (National Research University); M.F. Vladimirsky Moscow Region Research Clinical Institute

Dolgoprudny, Russia; Moscow, Russia

L. E Ruppel

Moscow Institute of Physics and Technology (National Research University)

Dolgoprudny, Russia

D. A Minakov

MIREA – Russian Technological University

Moscow, Russia

N. V Suvorov

MIREA – Russian Technological University

Moscow, Russia

P. V Ostroverkhov

MIREA – Russian Technological University

Moscow, Russia

Yu. L Vasil’ev

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Moscow, Russia

M. V Nikolaev

I.M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences

St. Petersburg, Russia

V. A Tsvelaya

Moscow Institute of Physics and Technology (National Research University); M.F. Vladimirsky Moscow Region Research Clinical Institute; ITMO University

Dolgoprudny, Russia; Moscow, Russia; St. Petersburg, Russia

K. I Agladze

Moscow Institute of Physics and Technology (National Research University); M.F. Vladimirsky Moscow Region Research Clinical Institute

Dolgoprudny, Russia; Moscow, Russia

M. A Grin

MIREA – Russian Technological University

Moscow, Russia

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