BENZOYLATED BISPIDONE: SYNTHESIS AND LOCAL ANAESTHETIC ACTIVITY

Abstract

Introduction. Local anaesthetics work by blocking voltage-gated sodium channels, which causes a temporary loss of sensation needed for many medical procedures. While novocaine, lidocaine, and trimecaine are effective, they have drawbacks such as short duration, possible toxicity, and tolerability problems. This study set out to create a complex of benzoylated 3-(3-butoxypropyl)-7-cyclopropanemethyl-substituted bispidone with β-cyclodextrin (LAC-5) and to compare its local anaesthetic effects with medicals using standard preclinical tests. LAC-5 was synthesised using Mannich condensation, oximation, O-benzoylation, and β-cyclodextrin complexation. Its structure was confirmed by methods such as infrared and nuclear magnetic resonance spectroscopies. Tests showed that LAC-5 has strong local anaesthetic effects, performing better than trimecaine, lidocaine, and novocaine in both infiltration and conduction anaesthesia models. In infiltration anaesthesia, LAC-5 achieved the maximum measurable depth of anaesthesia (index 36.0) at a 0.25% concentration, with a duration of complete anaesthesia of 56.66 min and a total duration of action of 76.66 min, exceeding the reference medications by up to 5.66- and 2.6-fold, respectively (p < 0.001). In conduction anaesthesia, LAC-5 produced a total duration of action of 160.0 ± 4.7 min, surpassing reference medications. Based on the results obtained, LAC-5 is recommended for comprehensive preclinical pharmacological evaluation, including assessment of acute toxicity, safety profile, and mechanism of action.