Abstract
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.
Highlights
IntroductionAntiarrhythmic drugs have been in use for over 100 years to prevent and treat heart rhythm disorder despite many limitations and adverse effects (Castro et al 2015)
The study aim was to identify essential elements of the antiarrhythmic action mechanism of tertiary and quaternary derivatives of Dimethylphenylacetamide
LKhT-3-00 like Lidocaine passes through the bi-lipid membrane (BLM) of the cardiac cell in an ionised form, whereas the quaternary derivative permeates cardiac cell membrane in an electro-neutral form
Summary
Antiarrhythmic drugs have been in use for over 100 years to prevent and treat heart rhythm disorder despite many limitations and adverse effects (Castro et al 2015). Their role of being the essential part of antiarrhythmic therapy inspires researchers to create novel molecules all over the world. The mechanism of action is the cornerstone, which determines the therapeutic effectiveness and safety profile of an antiarrhythmic drug. It might be defined as an assembly of functional transformations of intracellular homeostasis and extracellular interaction that determines the pharmacological property of a drug. The main reason for developing the substances was the short duration of Lidocaine therapeutic activity, which makes it impossible to administer the drug orally for prophylaxis (Collinsworth et al 1974)
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