On local anesthetic action of some dimethylacetamide compounds

Авторы

  • Andrei V. Novikov National Research Ogarev Mordovia State University
  • Ekaterina V. Blinova National Research Ogarev Mordovia State University, Sechenov University ORCID logo https://orcid.org/0000-0003-0050-0251
  • Elena V. Semeleva National Research Ogarev Mordovia State University
  • Karina M. Karakhanjan Sechenov University
  • Mikhail A. Mironov National Research Ogarev Mordovia State University
  • Dmirty S. Blinov All-Union Research Center for Safety of Biological Active Substances ORCID logo https://orcid.org/0000-0002-8385-4356
  • Yuliya S. Krainova National Research Ogarev Mordovia State University
  • Dmitry V. Pakhomov National Research Ogarev Mordovia State University
  • Olga V. Vasilkina National Research Ogarev Mordovia State University
  • Elena A. Samishina National Research Ogarev Mordovia State University

DOI:

https://doi.org/10.3897/rrpharmacology.4.31440

Аннотация

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.

Ключевые слова:

local anesthesia, dimethylacetamide compounds, terminal anesthesia, conduction, computational prediction, acute toxicity, isolated nerve

Вклад авторов

Andrei V. Novikov, National Research Ogarev Mordovia State University

Postgraduate student, Faculty Surgery Department. The author conducted experiments on animal models.

Ekaterina V. Blinova, National Research Ogarev Mordovia State University, Sechenov University

Doctor of Medical Sciences, Head of the Laboratory of Specific Pharmacological Activity, Professor. The author organized the project. Scopus

Elena V. Semeleva, National Research Ogarev Mordovia State University

Candidate of Medical Sciences, Associate Professor, Department of Public Health. The author conducted the statistic processing of the obtained data.

Karina M. Karakhanjan, Sechenov University

Postgraduate student, Department of the Operative Surgery. The author conducted the experiments on isolated nerves and prepared the manuscript for publising.

Mikhail A. Mironov, National Research Ogarev Mordovia State University

Assistant, the Department of the Hospital Surgery. The author conducted the experiments on animal models.

Dmirty S. Blinov, All-Union Research Center for Safety of Biological Active Substances

Doctor of Medical Sciences, Principal Researcher, Pharmacology Laboratory. The author designed the project, provided consulting support, and, finally, revised the manuscript. Scopus

Yuliya S. Krainova, National Research Ogarev Mordovia State University

Postgraduate student, Faculty Surgery Department. The author conducted the experiments on animal models.

Dmitry V. Pakhomov, National Research Ogarev Mordovia State University

Postgraduate student, Faculty Surgery Department. The author conducted the experiments on animal models as well as did the statistic processing of obtained data.

Olga V. Vasilkina, National Research Ogarev Mordovia State University

Candidate of Medical Sciences, Assistant Professor, Department of Hospital Surgery. The author conducted the experiments on isolated nerves and prepared the manuscript for publishing.

Elena A. Samishina, National Research Ogarev Mordovia State University

Candidate of Medical Sciences, Senior Researcher, Laboratory of Specific Pharmacological Aactivity. The author conducted the experiments on animal models and prepared the manuscript for publishing.

Загрузки

Опубликован

02.12.2018

Как цитировать

Novikov AV, Blinova EV, Semeleva EV, Karakhanjan KM, Mironov MA, Blinov DS, Krainova YS, Pakhomov DV, Vasilkina OV, Samishina EA (2018) On local anesthetic action of some dimethylacetamide compounds. Research Results in Pharmacology 4(4): 1–8. https://doi.org/10.3897/rrpharmacology.4.31440

Выпуск

Том 4 № 4 (2018)

Раздел

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