Redox Behavior of Central-Acting Opioid Tramadol and Its Possible Role in Oxidative Stress

Abstract

Tramadol (TRA) is a central-acting opioid whose biological activities are achieved by interaction with several bodily receptors such as μ-opioid receptors. Considering that central-acting drugs may promote oxidative stress, which could lead to neurodegeneration, this work reported the investigation of the redox behavior of TRA by electrochemical and semi-empirical quantum chemistry approaches (i.e., voltammetry and extended Hückel method—EHM) in order to study TRA pro-oxidant features. Electrochemical results showed that TRA exhibited two anodic peaks, namely: 1a at Ep1a ≈ +0.03 V and 2a at Ep2a ≈ +0.8 V; and a cathodic peak at Ep1c ≈ −0.01 V, whereas the quantum chemistry model suggested that the highest occupied molecular orbital n = 0 (HOMO-0) was associated with the tertiary amine in the TRA molecule, while HOMO-1 and the lowest unoccupied molecular orbital n = 0 (LUMO-0) were associated with the aromatic benzene ring. The findings were then used to propose an electrooxidation pathway according to the observations and compared to the literature, which further offered hints about TRA’s pro-oxidant nature. In conclusion, the work reported herein shows that voltammetric and semi-empirical quantum chemistry approaches can be correlated to investigate the redox behavior of CNS-acting compounds.