Dextromethorphan (DXM) & MAOI
Dextromethorphan (DXM) is a dissociative drug and cough suppressant that works by acting on the brain's cough center to reduce the urge to cough. Its exact mechanism of action is not fully understood, but it is believed to involve several different mechanisms.
Research suggests that DXM primarily operates by blocking N-methyl-D-aspartate (NMDA) receptors, which are a type of glutamate receptor responsible for excitatory neurotransmission in the central nervous system. This blocking action interferes with the transmission of excitatory signals. Interestingly, this mode of action shares similarities with ketamine and PCP.
In addition to its primary mechanism, DXM acts as a nonselective serotonin reuptake inhibitor, an antagonist of alpha-3 beta-4 nicotinic receptors, and an agonist of sigma-1 receptors.
Despite being a derivative of morphine, DXM exhibits the properties of a very weak μ-opioid agonist, and then, under the condition of large dosages.
But even without this, we see that DKSM shows a fairly broad activity on different receptor systems, which can lead to various side effects and potential risks when combined.
MAOIs, or Monoamine Oxidase Inhibitors, are a class of medications primarily used for the treatment of depression. They work by inhibiting the activity of the enzyme called monoamine oxidase (MAO), specifically MAO-A and MAO-B. These enzymes are responsible for breaking down neurotransmitters like serotonin, norepinephrine, and dopamine. By inhibiting MAO, MAOIs prevent the rapid degradation of these neurotransmitters, leading to increased levels in the brain.
Here is a list of some MAOIs:
- Selegiline (Emsam, Eldepryl) is an irreversible MAO-B inhibitor.
- Rasagiline (Azilect) is a selective MAO-B inhibitor.
- Moclobemide (Aurorix) is a reversible MAOI-A inhibitor.
- Isocarboxazid ( Marplan): nonselective MAOI.
- Phenelzine (Nardil): nonselective MAOI.
- Tranylcypromine (Parnate): Tonselective MAOI.
MAOIs allow higher concentrations of neurotransmitters to accumulate in the synaptic cleft, the gap between nerve cells. This increased availability of neurotransmitters enhances their signaling and transmission between nerve cells, which can have mood-elevating effects.
MAOIs, particularly MAO-A inhibitors, are effective in increasing serotonin levels. Serotonin is involved in regulating mood, appetite, and sleep, among other functions. By inhibiting the breakdown of serotonin, MAOIs ensure that it remains active in the brain for a longer duration, potentially alleviating depressive symptoms.
MAOIs also impact the levels of other neurotransmitters like norepinephrine (noradrenaline) and dopamine. Norepinephrine is associated with attention, focus, and arousal, while dopamine plays a role in motivation, pleasure, and reward. By inhibiting MAO, MAOIs help maintain higher levels of these neurotransmitters, which may contribute to their antidepressant effects.
When taken together, certain interactions can occur between dextromethorphan and MAOIs, leading to potential side effects and dangers.
The main concern with combining DXM and MAOIs is the risk of serotonin syndrome. MAOIs inhibit the breakdown of serotonin, increasing its levels in the brain. Dextromethorphan can also affect serotonin levels by inhibiting its reuptake.
When both DXM and MAOIs are present in the body, there can be an excessive accumulation of serotonin, leading to serotonin syndrome. This condition can manifest as agitation, confusion, rapid heartbeat, high blood pressure, dilated pupils, tremors, and in severe cases, it can be life-threatening.
In addition, the complex action of both DXM and MAOIs on other neurotransmitter systems can also lead to acute, unpredictable and life-threatening reactions.
All things considered, we recommend avoiding this combination under any conditions.
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