Treatment with dextromethorphan improves endothelial function, inflammation and oxidative stress in male heavy smokers

Background: Dextromethorphan (DM) is reported to reduce the inflammation-mediated degeneration of dopaminergic neurons. Objective: The goal of this study was to test if DM can improve the endothelial dysfunction and inflammatory markers in heavy smokers. Patients and methods: Forty habitual smoking healthy male volunteers (mean age, 31.5±1.4 years) were randomly given either DM (120 mg day^-1) or a placebo for 6 months. We determined endothelial function using the brachial artery diameter changes in flow-mediated dilatation (FMD) and measured their inflammatory and oxidative markers. A sex-and-age matched non-smoking group (n = 20) was compared as normal parameters. Results: Habitual smokers showed impaired baseline endothelial function in FMD (smoking vs. non-smoking: 6.3±1.8 vs. 10.2±2.3% respectively, P < 0.01). Without change in smoking behavior, lipid and metabolic parameters, a significant increase in FMD was found in the DM-treated group (32%), accompanied by a decrease in high-sensitivity C-reactive protein (hs-CRP), phospholipase A₂, matrix metalloproteinase-3, interleukin 6 (IL-6) and tumor necrosis factor-α receptor II (TNF-α RII) (all P < 0.05), but unchanged in von Willebrand factor (VWF)and plasminogen activator inhibitor-1 (PAI-1). An increase in plasma glutathione peroxidase and a decrease in spot urinary excretion of 8-epi-prostaglandin F_2a were found in DM-treated smokers. Conclusions: Our study suggests that a 6-month treatment with DM can improve endothelial function and attenuate vascular oxidative stress and inflammation markers in habitual smokers.