On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives

Авторы

  • Mohamed Hameed Salem Yahya Ogarev Mordovia State University
  • Nikolay A. Kurganov Ogarev Mordovia State University
  • Ekaterina V. Blinova Ogarev Mordovia State University ORCID logo https://orcid.org/0000-0003-0050-0251
  • Elena V. Semeleva Ogarev Mordovia State University
  • Arkadiy B. Lebedev Ogarev Mordovia State University
  • Dmirty S. Blinov Ogarev Mordovia State University ORCID logo https://orcid.org/0000-0002-8385-4356
  • Andrei V. Novikov Ogarev Mordovia State University

DOI:

https://doi.org/10.3897/rrpharmacology.4.25112

Аннотация

Abbreviations: AC – acetylcholyne; AF – atrial fibrillation; AP – action potential; BLM – bi-lipid membrane; DPA -Dimethylphenylacetamide; VA – ventricular arrhythmia

Introduction: The study aim was to identify essential elements of the antiarrhythmic action mechanism of tertiary and quaternary derivatives of Dimethylphenylacetamide.

Materials and Methods: The study was conducted in albino rats and mice of both sexes; isolated neurons of mollusc Limneastagnalis; and strips of rats’ right ventricle myocardium. Two compounds of Dimethylphenylacetamide LKhT-3-00 and LKhT-12-02 were studied. The cholynolytic property of the compounds was investigated by using a Schallek method in the authors’ modification. The adrenotropic activity of the derivatives was explored by Moore and Spear (1984), as well a by the method of catecholamine level detection in heart tissue. The permeability of derivatives through BLM was evaluated experimentally and theoretically. The derivatives’ influence on Na+-current was studied directly and indirectly.

Results and Discussion: Neither tertiary nor quaternary derivatives possess the cholynolytic property. LKhT-3-00 prevented an increase in the adrenaline concentration in the left ventricle myocardium. The compounds prevent catecholamine arrhythmia and conductivity disorders. LKhT-3-00 like Lidocaine passes through the BLM of the cardiac cell in an ionised form, whereas the quaternary derivative permeates cardiac cell membrane in an electro-neutral form. Lidocaine derivatives restrain acute ischemia-induced oxidative process growth in the cardiac muscle. Simultaneously, the LKhT-3-00 compound can activate antioxidant mechanisms and prevent acidosis and optimise the balance between [O2] and [CO2] concentrations in coronary dark blood. At a concentration of 10 mg/ml, although the derivatives reduce the amplitude of the leading edge of AP and its rate of increase, they do not, however, affect the duration of AP.

Conclusions: The compounds possess the Na+-blocking and cell-protecting properties. They do not affect K+-current through Kv4.3-channels.

Ключевые слова:

antiarrhythmic activity, Dimethylphenylacetamide derivatives, tertiary and quaternary compounds, mechanism of action, action potential, permeability, arrhythmia, catecholamine

Вклад авторов

Mohamed Hameed Salem Yahya, Ogarev Mordovia State University

Postgraduate Student.

Nikolay A. Kurganov, Ogarev Mordovia State University

Postgraduate Student.

Ekaterina V. Blinova, Ogarev Mordovia State University

Doctor of Medical Sciences, Professor. Scopus

 

Elena V. Semeleva, Ogarev Mordovia State University

PhD in Medicine, Associate Professor, Department of Public Health.

Arkadiy B. Lebedev, Ogarev Mordovia State University

PhD in Medicine, Senior Research Fellow, Centre for Novel Medication Research.

Dmirty S. Blinov, Ogarev Mordovia State University

Doctor of Medical Sciences, Principal Researcher, Centre for Novel Medication Research. Scopus

Andrei V. Novikov, Ogarev Mordovia State University

Postgraduate Student.

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Опубликован

28.03.2018

Как цитировать

Hameed Salem Yahya M, Kurganov NA, Blinova EV, Semeleva EV, Lebedev AB, Blinov DS, Novikov AV (2018) On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives. Research Results in Pharmacology 4(1): 1–9. https://doi.org/10.3897/rrpharmacology.4.25112

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