OBJECTIVES To study the local anesthetic activity in infiltration anesthesia of modified piperidine derivatives: LAS-134, LAS-174 and 175, LAS-189 and 190 (LAS - local anesthetic substance) and the relationship between the chemical structure and pharmacological activity.

METHODS

Local anesthetic activity of membranstabilizing agents in infiltration anesthesia was determined by the method of Bühlbring-Wide on guinea pigs.

RESULTS

LAS-134 (homologous of Kazkaine) is less toxic by 1.5 times, in 0.1% solutions by the strength of anesthesia statistically exceeds Kazkaine, it lasts 1.24 times longer. 0,25% solutions LAS-134 is also more active than Kazkaine in all parameters. The introduction of 1 additional methylene group at the nitrogen atom of the piperidine ring leads to a significant decrease in toxicity and to increase in local anesthetic activity. Analogue of Kazkaine LAS-175 on the strength of anesthetic effect is equal to Kazkaine, LAS-174 exceeds that Kazkaine. The parameter of complete anesthesia LAS-174 and 175 is slightly higher than Kazkaine, the total duration significantly exceeds 1.5 and 2.1 times, respectively. The "weighting" of radical at the 4th carbon atom leads to intensification of pharmacological effect (propyl radical against amyl). Homologues of Kazkaine LAS-189 and 190 in infiltration anesthesia have anesthesia index higher than Kazkaine, on the total duration of anesthesia they exceed Kazkaine and are some more active in duration of complete anesthesia. Substitution of the hydrogen atom for the cyclopropane radical, as well as the "weighting" of the radical at the 4-th carbon atom (propyl to phenyl) increases activity of compounds.

CONCLUSIONS

Thus, the introduction of additional radicals at the nitrogen atom, as well as at the 4-th carbon atom, contribute to an increase in local anesthetic activity.