Abstract
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.
Highlights
Materials and methodsOver the past decades, revolutionary changes in clinical practice, the creation and widespread introduction of new high-tech methods of diagnosis and treatment make new demands for a modern drug for local anesthesia (Chitilian et al 2016, Mennito 2016)
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
The local anesthetic activity of the derivatives on the models of conduction anesthesia was determined by tail-flick test in mice and sciatic nerve blockade model in rats (Ouchi et al 2013)
Summary
Materials and methodsOver the past decades, revolutionary changes in clinical practice, the creation and widespread introduction of new high-tech methods of diagnosis and treatment make new demands for a modern drug for local anesthesia (Chitilian et al 2016, Mennito 2016). Medical manipulations, which used to be impossible outside the hospital, have become routine for outpatient surgery and invasive diagnostics (Mennito 2016). The factor of the aging population, the extremely spread comorbidity, increasing requirements for drug safety, reduced cost of both a local anesthetic drug and medical equipment, as well as other resource costs associated with its use have great importance for the choice of a means and method of anesthesia at the present time (Forman 2010). Of particular importance when selecting a local anesthetic is the pharmacological characteristics, such as the rate of development of the effect, the depth of local anesthesia, the duration of action, and the speed of anesthesia recovery (Mennito 2016, Forman 2010). A short duration of the drug action, a relatively wide range of its adverse effects made pharmacologists and clinicians search for more optimal medicinal solutions in this area
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