Is methoxydine a new rapid acting antidepressant for the treatment of depression in alcoholics?

Methoxydine, a dissociative anaesthetic in the arylcyclohexylamine class, pharmacodynamically resembles ketamine, a known rapid-acting antidepressant. Binding assays indicate it is an uncompetitive NMDA receptor antagonist about as potent as ketamine but less potent than PCP. Unlike ketamine, methoxydine also inhibits reuptake of dopamine, serotonin, and noradrenaline and acts as an agonist at sigma-1, sigma-2, and opioid receptors. The hypothesis is that methoxydine could produce rapid antidepressant effects in depressed patients at high risk of suicide, including depressed alcoholics.

Study at a glance

Abstract

Methoxydine is a dissociative anaesthetic belonging to the arylcyclohexylamine class. This substance shows pharmacodynamic similarities with ketamine, a medication with demonstrated rapid-acting antidepressant effects. Like ketamine, results of binding assays have shown that methoxydine is an uncompetitive antagonist of NMDA receptor approximately as potent as ketamine, but less potent than PCP. Furthermore, unlike ketamine, it acts as a dopamine, serotonin, and noradrenaline reuptake inhibitor as well as an agonist at sigma-1, sigma-2, and opioid receptors. The hypothesis is that methoxydine can produce rapid antidepressant effects in depressed patients with high risk of suicide, including depressed alcoholics.