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Background: To evaluate acute toxicity and local anaesthetic activity of a formulation containing a novel dimethylacetamide derivative, antioxidant, and vasoconstrictor in rats with chronic periodontitis., Methods: Novel anaesthetic dimethylacetamide-containing formulation LHT-15-32 was studied as 2% water solution. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of the upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats' gingival mucosa by induced chemiluminescence. Local changes were evaluated in periodontal tissue by morphological examination. Tissue IL-1 β , IL-10, and TNF-α concentration was quantitatively assessed by an enzyme-linked immunosorbent assay. LHT-15-31 Na-blocking activity was studied on isolated neurons of Limnaea stagnalis ' parapharyngeal ganglion. Isolated sciatic nerve of Rana radibunda was perfused with different concentrations of LHT-15-32 to assess its conductivity. Statistical analysis was used, and continuous variables were presented as mean ± square deviation. The normality of distribution was determined using ANOVA. Newman-Keuls parametric criterion was used for intergroup comparison. LD 50 indexes were calculated by probit analysis., Results: LHT-15-32 acute intravenous and subcutaneous toxicity was lower than that of its active substance. The formulation by infraorbital administration induced deep dental anaesthesia which lasted over 70 min and activated the local antioxidant defense system and decreased IL-1 β level in gingival tissue. LHT-15-32 triggered tissue reparation around the impacted upper molar in rats assessed five days after administration. At 10 -6 to 10 -3  M concentration, LHT-15-32 inhibited sciatic nerve conductivity and blocked Na + channels of isolated neurons in a dose-dependent manner., Conclusions: The formulation may be considered as an effective and safe approach to anaesthetize upper molars with periodontitis., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2020 Ekaterina V. Blinova et al.)

Novel anaesthetic formulation LHT-15-32 was studied. The experimental study involved 66 white mice, 15 Rana radibunda frogs and 50 male Sprague Dawley rats. Its acute intravenous and subcutaneous toxicity was determined in mice. Pain sensitivity threshold of upper second molar was determined in rats with experimental periodontitis. Oxidative stress activity and total antioxidant capacity were determined in rats' gingival mucosa by induced chemiluminescence. Tissue IL-1β, IL-10 and TNF-a concentration was quantitatively assessed by ELISA. LHT-15-32 Na-blocking activity was studied on isolated neurons of Limnea stagnalis para-pharyngeal ganglion. Rana radibunda isolated sciatic nerve was perfused with LHT-15-32 to assess its conductivity. LHT-15-32 acute intravenous and subcutaneous toxicity was lower then that of its active substance LHT-4-00. The formulation infraorbital administration induced deep dental anaesthesia lasted longer than 70 min, activated local antioxidant defence system and decreased IL-1β level in gingival tissue. At 10 -6 to 10 -3 M LHT-15-32 inhibited sciatic nerve conductivity and blocked Na + -channels of isolated neurons in dose-dependent manner. LHT-15-32 proved to be less toxic than active substance and lidocaine. The agent provides deep and prolonged anesthesia of the upper molar of rats in chronic apical periodontitis, lowers tissue concentration of pain cascade cytokines and oxidative stress activity and suppresses the action potential amplitude of a sensory nerve due to Na-blocking activity.

The effect of a cerebroprotective agent magnesium bis-aminoethanesulfonate (laboratory code FS-LKhT-317) on intracellular calcium concentration was studied by the fluorescent imaging technique on neuroglial cell culture from Spraque-Dawley rat hippocampus. The substance produced a pronounced inhibitory effect and suppressed NMDA receptor activity in concentrations of ≥50 μM. The observed effects were reversible or partially reversible and were detected by a decrease in Ca 2+ signal amplitude in neurons in response to NMDA applications in a Mg 2+ -free medium and by inhibition of Ca 2+ pulses in magnesium-free medium (elimination of magnesium block).