Assessment of impact of a new derivative 2-(diethylamino)-N-(o-toluyl) acetamide, manifesting antiarrhythmic effect in heart rhythm disorders of peripheral origin, on cardiovascular system

Abstract

Objective. To study the effect of a new derivative of arylamides of aminocarboxylic acids, which has a high antiarrhythmic activity on the state of the cardiovascular system.

Materials and methods. To study the antiarrhythmic activity of the compound, the experiment was carried out on a model of arrhythmia caused by intravenous administration of aconitine. The effect was evaluated by its ability to prevent the occurrence of arrhythmia or to prolong the survival time of animals. In addition, an analysis of the electrocardiogram of awake rats and rabbits was carried out. The test compound and the comparison drug, lidocaine, were intravenously administered to animals in effective antiarrhythmic doses.

Results. Diethylaminoacetic acid ortho-toluidide nitrate under conditions of aconitine arrhythmia shows a pronounced antiarrhythmic effect; under its influence, there is a statistically significant reduction in the duration of arrhythmia attacks in animals by 2.4 times compared with the control as well as protection from death. The compound does not change the parameters of electrocardiogram of animals, no statistically significant differences from the control results were found.

Conclusions. 1. A new compound, diethylaminoacetic acid ortho-toluidide nitrate, exhibits a pronounced antiarrhythmic effect. Probably, it can be attributed to class IB antiarrhythmic drugs, since it exhibits high activity on calcium chloride and aconitine models of arrhythmia.

2. Given that the studied compound combines high antiarrhythmic activity with no negative effect on ECG parameters, a drug based on it can be used as an effective antiarrhythmic drug.

Keywords

arrhythmia / lidocaine / aconitine model of arrhythmia / electrocardiogram / effective antiarrhythmic dose

References

[1] Shal′nova S.A., Deyev S.A., Oganov R.G. Factors affecting mortality from cardiovascular diseases in the Russian population. Kardiovaskulyarnaya terapiya i profilaktika 2018; 1: 4–9 (in Russian).

[2] Шальнова С.А., Деев С.А., Оганов Р.Г. Факторы, влияющие на смертность от сердечно-сосудистых заболеваний в российской популяции. Кардиоваскулярная терапия и профилактика 2018; 1: 4–9.

[3] Zaman S., Goldberger J.J., Kovoor P. Sudden death risk-stratification in 2018–2019: the old and the new. Heart, Lung and Circulation 2019; 1: 57–64.

[4] Bokeriya O.L., Biniashvili M.B. Sudden cardiac death and ischemic heart disease. Annaly aritmologii 2013; 2: 69–79 (in Russian).

[5] Бокерия О.Л., Биниашвили М.Б. Внезапная сердечная смерть и ишемическая болезнь сердца. Анналы аритмологии 2013; 2: 69–79.

[6] Shvalev V.N., Rogoza A.N., Tarskiy N.A. Sudden cardiac death and morphofunctional diagnosis of previous age-related neurodystrophic changes in the body. Tikhookeanskiy meditsinskiy zhurnal 2017; 1: 42–51 (in Russian).

[7] Швалев В.Н., Рогоза А.Н., Тарский Н.А. Внезапная сердечная смерть и морфофункциональная диагностика предшествующих возрастных нейродистрофических изменений организма. Тихоокеанский медицинский журнал 2017; 1: 42–51.

[8] Doshitsin V.L. Controversial issues of drug therapy for cardiac arrhythmias. Kremlevskaya meditsina. Klinicheskiy vestnik 2015; 3: 147–150 (in Russian).

[9] Дошицин В.Л. Спорные вопросы лекарственной терапии аритмий сердца. Кремлевская медицина. Клинический вестник 2015; 3: 147–150.

[10] Guidelines for conducting preclinical studies of medicinal products. Pod red. A.N. Mironova. Moscow: Grif i K 2012; 944 (in Russian).

[11] Руководство по проведению доклинических исследований лекарственных средств. Под ред. А.Н. Миронова. М.: Гриф и К 2012; 944.

[12] Boronenkova E.S. Antiarrhythmic activity of new isoquinoline derivatives: avtoref. dis. … kand. biol. nauk. Tomsk 1996; 21 (in Russian).

[13] Бороненкова Е.С. Антиаритмическая активность новых производных изохинолина: автореф. дис. … канд. биол. наук. Томск 1996; 21.

[14] Prozorovskiy V.B. Statistical processing of the results of pharmacological studies. Psikhofarmakologiya i biologicheskaya narkologiya 2007; 3–4: 2090–2120 (in Russian).

[15] Прозоровский В.Б. Статистическая обработка результатов фармакологических исследований. Психофармакология и биологическая наркология 2007; 3–4: 2090–2120.

[16] Rudakova I.P., Gashkova O.V., Chekryshkina L.A. Study of the arrhythmogenic effect of a new derivative of diethylamino-acetic acid orthotoluidide, which has shown antiarrhythmic activity. Razrabotka i registratsiya lekarstvennykh sredstv 2015; 2 (11): 204–206 (in Russian).

[17] Рудакова И.П., Гашкова О.В., Чекрышкина Л.А. Исследование аритмогенного действия нового производного ортотолуидида диэтиламиноуксусной кислоты, проявившего антиаритмическую активность. Разработка и регистрация лекарственных средств 2015; 2 (11): 204–206.

[18] Bigus S.K., Galenko-Yaroshevskiy P.A., Suzdalev K.F. Acute toxicity and antiarrhythmic properties of the indole derivative SS-68 under conditions of aconitine and calcium chloride models of arrhythmias. Novyye tekhnologii 2012; 4: 236–238 (in Russian).

[19] Бигус С.К., Галенко-Ярошевский П.А., Суздалев К.Ф. Острая токсичность и антиариитмические свойства производного индола SS-68 в условиях аконитиновой и хлоридкальциевой моделей аритмий. Новые технологии 2012; 4: 236–238.

[20] Pathophysiology of the cardiovascular system. Pod red. L. Lilli; per. s angl. 3-e izd., ispr. i pererab. Moscow: BINOM. Laboratoriya znaniy 2010; 672 (in Russian).

[21] Патофизиология сердечно-сосудистой системы. Под ред. Л. Лилли; пер. с англ. 3-е изд., испр. и перераб. М.: БИНОМ. Лаборатория знаний 2010; 672.

RIGHTS & PERMISSIONS

Rudakova I.P., Gashkova O.V.