Derivatives of methoxetamine and major methoxetamine metabolites potently block NMDA receptors.
Journal of pharmacological sciences December 1, 2022 Tomohiko Irie, Yuta Yanase, Yosuke Demizu et al. 2 citations
Methoxetamine and its derivatives deoxymethoxetamine and methoxisopropamine, sold online as designer drugs, block N-methyl-D-aspartate receptors (NMDARs) in the brain. Computer docking simulations suggested these compounds interact with NMDARs. Using patch-clamp recordings from mouse neurons expressing NMDARs, the half-maximal inhibitory concentrations (IC50s) were determined: methoxetamine 0.524 μM, deoxymethoxetamine 0.679 μM, methoxisopropamine 0.661 μM, and the methoxetamine metabolites N-desethyl methoxetamine 1.649 μM and O-desmethyl methoxetamine 0.227 μM. All acted as potent NMDAR blockers, indicating that deoxymethoxetamine and methoxisopropamine may cause harm by blocking these receptors, and the metabolites may contribute to adverse effects when methoxetamine is metabolized.