PhD Scientific Days 2026

Poster Session 3.W - Pharmaceutical Sciences and Health Technologies

Effect of Tolperisone on Monoamine Oxidase Activity

Name of the presenter

Lincmajer, Zoltan

Institute/workplace of the presenter

Department of pharmacodynamics

Authors

Zoltan Lincmajer¹, Amira Al-Khrasani¹, Éva Szökő¹
1: Department of pharmacodynamics

Text of the abstract

Introduction: Tolperisone is a centrally acting muscle relaxant that has been used in clinical practice for decades. Previous studies from our research group demonstrated that tolperisone effectively attenuates neuropathic pain in a rat model. Investigation of its mechanism of action has identified potent inhibition of voltage-gated sodium channels, along with weaker inhibition of calcium channels and monoamine uptake.

Aim: The aim of the present study was to characterize the effect of tolperisone on monoamine oxidase (MAO) activity.

Methods: MAO activity was measured in rat brain extract using a fluorescence-based assay. Hydrogen peroxide generated during enzymatic activity was detected using horseradish peroxidase and Amplex Red. Pargyline-sensitive hydrogen peroxide formation was considered MAO-specific activity. Serotonin and phenylethylamine were used as selective substrates for MAO-A and MAO-B, respectively.

Results: Tolperisone inhibited hydrogen peroxide formation in a concentration-dependent manner with both substrates, indicating inhibition of both MAO isoforms. Half-maximal inhibition was achieved at 77.30 µM (95% CI: 65.18–86.7) with serotonin and at 122.1 µM (95% CI: 102.4–171.4) with phenylethylamine. These results revealed a mild but statistically significant preference toward MAO-A inhibition (p<0.0001). Because MAO activity was quantified indirectly through hydrogen peroxide production, potential assay interference due to antioxidant effects was also evaluated. Tolperisone did not reduce standard hydrogen peroxide concentrations, suggesting that the observed inhibition was not attributable to antioxidant activity. Additional enzyme kinetic experiments indicated an uncompetitive inhibition mechanism.

Conclusions: Our findings suggest that tolperisone possesses non-selective MAO inhibitory activity with a modest preference toward MAO-A. This property may contribute to its previously observed antiallodynic effect by increasing monoamine availability and enhancing descending pain inhibitory pathways. The uncompetitive nature of inhibition also raises the possibility that its pharmacological effect may become more pronounced under conditions of increased enzymatic activity.

Funding: Semmelweis 250+ and Gedeon Richter Talentum Excellence PhD Scholarships are appreciate.