Methoxetamine is a dopamine reuptake inhibitor, a nicotinic acetylcholine receptor antagonist, an uncompetitive NMDA channel blocker, a dopamine D2 receptor agonist, and a mu-opioid agonist, according to the current SAR as well as subjective reports consistent with this effect profile.
Methoxetamine has in the past demonstrated the ability to cause serious problems in conjunction with serotonin releasers; the combination of methoxetamine and MDAI (which is a serotonin releaser with no other effects to speak of) lead to the death of one unfortunate Swede who had taken only a moderate dose of both compounds. Simply put: the combination of methoxetamine and a serotonin releaser appears to be extremely dangerous!
It is therefore highly inadvisable to combine methoxetamine with any serotonin releaser or suspected serotonin releaser, or with DXM (a very potent serotonin reuptake inhibitor, though not a releaser) -- this includes MDMA, 6-APB, AMT, MDAI to name a few.
The increasing number of these reports suggest that this interaction is indeed quite real; it is possible however unlikely that methoxetamine acts in some way to inhibit the breakdown of serotonin, via monoamine oxidase inhibition or otherwise. Methoxetamine and the other methoxylated arylcyclohexylamines (4-MeO-PCP, 3-MeO-PCP, 3-MeO-PCE) bear some structural similarity to the infamous PMA and the less-well-known MAOI para-methoxy-phenethylamine (PMPEA). The appearance of unexpected effects is always a possibility when testing a new compound especially testing in vivo with no pre-existing in vitro binding data. To combine these with other compound increases the risk of ingestion substantially.
