Membrane Mechanisms of Antiarrhythmic Effect of Quaternidine

Balashov, V. P.; Блинов, Д. С.; Kazachenko, V.N.; Astashev, Maxim E.; Agenosova, O. G.

doi:10.1007/s10517-005-0379-y

Cited by 5 publications

(6 citation statements)

References 2 publications

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“…3*HCl, is a local anaesthetic that has antiarrhythmic effects. [15][16][17] In the present study, new ionic compounds were prepared via N-alkylation of tolperisone, diphenhydramine and trimecaine with alkyl halides (Scheme 1, Table 1). Since some of the synthesized ionic compounds have been proven to stimulate plant growth, [18,19] the ecotoxicity and myelostimulating [20] data for these substances is of great importance.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Ecotoxicological Studies of Ionic Compounds Based on Tolperisone, Diphenhydramine and Trimecaine

et al. 2020

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Ionic compounds have been of global interest since stepping into a mature field of research. The aim of this study was to synthesize novel and known ionic compounds via the N‐alkylation process and fully characterize them by elemental analysis and infrared (IR) and nuclear magnetic resonance (NMR) spectroscopy. Investigation of the influence of the alkyl chain length and the charge of the cation on the ecotoxicity of 11 new and known ionic compounds based on tolperisone, diphenhydramine and trimecaine was investigated with the use of luminescence inhibition assay. To give information about the ecotoxicity of these new ionic compounds, the acute toxicity dataset of each compound was determined using Aliivibrio fischeri bacteria as a biomodel. According to the obtained results, the studied compounds could be considered non‐harmful to Aliivibrio fischeri. A quantitative structure–activity relationship (QSAR) study was carried out with the aim of modelling the observed behaviour and providing a prediction basis for ecotoxicity towards Aliivibrio fischeri.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Ecotoxicological Studies of Ionic Compounds Based on Tolperisone, Diphenhydramine and Trimecaine

et al. 2020

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“…Recently, studies focusing on lidocaine (dimethylacetamide) derivatives have intensified in Russia. In a series of studies, their antiarrhythmic medication (Blinov and Kostin 2003;Blinov et al 2014;Sernov et al 2005) and the anti-ischemic (Kostin et al 2003) activities were studied, and it was shown that the derivatives exceed their structural ancestor both by duration and by efficiency in experimental animals (Blinova et al 2015) and in vitro (Balashov et al 2005). All this served as the basis for assuming that this group of amino acid-substituted and quaternary derivatives of dimethylacetamide had a local anesthetic activity, which determined the relevance of this study.…”

Section: Introductionmentioning

confidence: 99%

On local anesthetic action of some dimethylacetamide compounds

Новиков¹,

Blinova²,

Семелева³

et al. 2018

RRP

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The study aim was to explore local anesthetic properties of some tertiary and quaternary derivatives of dimethylacetamide. Materials and methods. The study was performed on white laboratory mice and rats of both sexes, male Agouti guinea pigs, and isolated sciatic nerves of lake frog. In the focus of the study there were two quaternary and eight tertiary compounds of dimethylacetamide with substituted anion with some amino and carbonic acids residue. A local anesthetic property was predicted by computational analysis. Acute toxicity of the most promising substances was studied in mice through subcutaneous route. Local anesthetic activity of tertiary compounds LKhT-3-00, LKhT-4-00 and quaternary LKhT-12-02 was studied on models of terminal, infiltration and conduction anesthesia. The influence of substances on mixed nerve conduction was investigated on lake frog’s isolated sciatic nerves. Results and discussion. The greatest probability of the local anesthetic activity during computational analysis was estimated for the tertiary derivatives of dimethylacetamide LKhT-3-00 and LKhT-4-00 and for the quaternary compound LKhT-12-02. According to their toxicological profile, the compounds belong to moderately toxic substances (class 3). On the model of terminal and infiltration anesthesia, substances LKhT-3-00 and LKhT-4-00 at concentrations of 0.5-1% rapidly cause deep and prolonged anesthesia. On the models of conduction anesthesia, the quaternary derivative of dimethylacetamide LKhT-12-02 has the greatest analgesic effect. The duration of the effect of the substance is over 3 hours. All the investigated compounds block sciatic nerve conduction. The longest effect is registered for LKhT-12-02. Conclusions. Dimethylacetamide derivatives at concentrations of 0.5-1.0% exhibit a local anesthetic activity, and are effective for terminal, conduction and infiltration anesthesia. Their effect is due to blockade of nerve conduction.

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“…Moreover, they would lose their antiarrhythmic property. In addition, it should be emphasised that an increased effect duration is accompanied by the molecule haemodynamic profile optimisation (Balashov et al 2005).…”

Section: Introductionmentioning

confidence: 99%

“…Quaternary DPA derivatives were produced by targeting the nitrogen of the aliphatic fragment of the molecule by analogy with developing a national antiarrhythmic drug quaternin, which is a quaternary allylmorpholinic derivative of Trimethylphenylacetamide (Balashov et al 2005). The new substance appeared to be more active than Lidocaine and possessed a promising antiarrhythmic effect.…”

Section: Introductionmentioning

confidence: 99%

On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives

Yahya¹,

Kurganov²,

Blinova³

et al. 2018

RRP

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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.

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Membrane Mechanisms of Antiarrhythmic Effect of Quaternidine

Cited by 5 publications

References 2 publications

Synthesis and Ecotoxicological Studies of Ionic Compounds Based on Tolperisone, Diphenhydramine and Trimecaine

Synthesis and Ecotoxicological Studies of Ionic Compounds Based on Tolperisone, Diphenhydramine and Trimecaine

On local anesthetic action of some dimethylacetamide compounds

On mechanism of antiarrhythmic action of some dimethylphenylacetamide derivatives

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