Novel ketamine and phencyclidine analogues sold as designer drugs bind with high affinity to the same NMDA receptor site as the parent compounds, based on radioligand binding assays conducted through a national screening program. Methoxetamine and 3-MeO-PCE, along with the 3- and 4-methoxy analogues of phencyclidine, all showed strong affinity for the PCP-site on the glutamate NMDA receptor. Methoxetamine and phencyclidine and its analogues also bound appreciably to the serotonin transporter, while the PCP analogues had high affinity for sigma receptors. NMDA receptor antagonism likely explains their dissociative and psychotomimetic effects in humans; additional receptor actions may contribute to side effects.
Two widely marketed novel psychoactive drugs, alpha-methyl-tryptamine and 5-methoxy-N,N-diallyl-tryptamine, were analyzed for their chemical structure and binding to serotonin receptor subtypes. These tryptamine-derived compounds, sold without restriction, can cause psychosis and hallucinations that may lead to injury or death. The study elucidates their structures and receptor binding profiles, providing insight into their pharmacological actions.