The serotonin receptor agonist 5-methoxy-N,N-dimethyltryptamine facilitates noradrenaline release from rat spinal cord slices and inhibits monoamine oxidase activity.

The compound 5-methoxy-N,N-dimethyltryptamine (MeODMT) strengthens noradrenergic signaling in the rat spinal cord through two distinct mechanisms: it facilitates the release of noradrenaline triggered by electrical stimulation and inhibits the breakdown of noradrenaline by monoamine oxidase (MAO), preferentially the A-type enzyme. The effect on basal noradrenaline outflow disappeared when MAO was blocked by pargyline, while the effect on evoked release was absent in the presence of metitepine or phentolamine. These findings indicate that MeODMT acts both as a release enhancer and a metabolism inhibitor to boost noradrenaline activity.

Study at a glance

Abstract

1. The influences of the purported serotonergic agonist 5-methoxy-N,N-dimethyltryptamine (MeODMT) on noradrenaline release and metabolism were investigated in a rat spinal cord release model and a monoamine oxidase (MAO) assay. 2. MeODMT inhibited the basal outflow of tritium from rat spinal cord slices preincubated with [3H]noradrenaline and enhanced the electrically-evoked overflow. 3. Effects on basal outflow were not observed, when monoamine oxidase (MAO) was inhibited by pargyline. Effects on the evoked overflow were not observed in the presence of metitepine or phentolamine. 4. Preferential inhibition by MeODMT of MAO A-type enzyme activity was found in a direct assay. 5. The results provide evidence for two different effects by which MeODMT reinforces noradrenergic neurotransmission in the rat spinal cord: facilitation of stimulation-evoked noradrenaline release and inhibition of noradrenaline metabolism by MAO inhibition.