On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives
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 quater...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Belgorod National Research University
2018-03-01
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| Series: | Research Results in Pharmacology |
| Online Access: | https://rrpharmacology.pensoft.net/article/25112/download/pdf/ |
| _version_ | 1797431664287154176 |
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| author | Mohamed Hameed Salem Yahya Nikolay Kurganov Ekaterina Blinova Elena Semeleva Arkadiy Lebedev Dmirty Blinov Andrei Novikov |
| author_facet | Mohamed Hameed Salem Yahya Nikolay Kurganov Ekaterina Blinova Elena Semeleva Arkadiy Lebedev Dmirty Blinov Andrei Novikov |
| author_sort | Mohamed Hameed Salem Yahya |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T09:48:29Z |
| format | Article |
| id | doaj.art-ff6174099f064feeb8100d278dcc2473 |
| institution | Directory Open Access Journal |
| issn | 2658-381X |
| language | English |
| last_indexed | 2024-03-09T09:48:29Z |
| publishDate | 2018-03-01 |
| publisher | Belgorod National Research University |
| record_format | Article |
| series | Research Results in Pharmacology |
| spelling | doaj.art-ff6174099f064feeb8100d278dcc24732023-12-02T00:27:11ZengBelgorod National Research UniversityResearch Results in Pharmacology2658-381X2018-03-01411910.3897/rrpharmacology.4.2511225112On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivativesMohamed Hameed Salem Yahya0Nikolay Kurganov1Ekaterina Blinova2Elena Semeleva3Arkadiy Lebedev4Dmirty Blinov5Andrei Novikov6Ogarev Mordovia State UniversityOgarev Mordovia State UniversityOgarev Mordovia State UniversityOgarev Mordovia State UniversityOgarev Mordovia State UniversityOgarev Mordovia State UniversityOgarev Mordovia State UniversityAbbreviations: 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.https://rrpharmacology.pensoft.net/article/25112/download/pdf/ |
| spellingShingle | Mohamed Hameed Salem Yahya Nikolay Kurganov Ekaterina Blinova Elena Semeleva Arkadiy Lebedev Dmirty Blinov Andrei Novikov On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives Research Results in Pharmacology |
| title | On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives |
| title_full | On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives |
| title_fullStr | On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives |
| title_full_unstemmed | On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives |
| title_short | On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives |
| title_sort | on mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives |
| url | https://rrpharmacology.pensoft.net/article/25112/download/pdf/ |
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