In Silico Study of Morphine-Like Effects of Ethanol Intake: Docking of Acetaldehyde Conjugates with Monoamines tothe Mu-Opioid Receptor

Abstract

Acetaldehyde produced after the ethanol intake forms conjugates with monoamines. Those conjugates are thought to be able to bind mu-opioid receptors and cause morphine-like effects. The aim of this study was to check the ability of acetaldehyde conjugates with dopamine (salsolinol), serotonin, tryptamine and tryptophan, as well as their enantiomers and derivatives to bind mu-opioid receptor structure available in the Protein Data Bank (www.pdb.org) using the Docking Server (www.dockingserver.com) and the FlexX method. The results showed that N-methyl-R-salsolinol, unlike its stereoisomer, is the most potent agonist of the mu-opioid receptor. The strength of morphine-like effect observed after alcohol intake should directly depend on the rate of R-salsolinol formation and N-methylation, but it should show an inverse dependence on the rate of N-methyl-R-salsolinol dehydrogenation. It was found that an N-methylated and dehydrogenated derivative of the acetaldehyde conjugate with tryptophan was another potent agonist of the mu-opioid receptor. Other compounds checked in this study were shown to act as antagonists and not agonists of the mu-opioid receptor.