MAO inhibitor: meperidine toxicity


The original antidepressants, phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine (Parnate) are all irreversible inhibitors of MAO-A and MAO-B, leading to pronounced effects on metabolism of endogenous (5-HT, NE, and DA) and exogenous (tyramine) monoamines. Selegeline is a selective MAO-B inhibitor – serotonin is deaminated by MAO-A (MAO-B primarily breaks down dopamine and phenethylamine), so the risk of serotonin syndrome is lower (unless high doses of selegiline are used, in which case MAO-A inhibition may occur).

All phenylpiperidine opioids (meperidine, methadone, tramadol) are weak serotonin reuptake inhibitors and can lead to serotonin syndrome (confusion, fever, diaphoresis, shivering, ataxia, myoclonus, hyperreflexia, and death) caused by excessive serotonergic stimulation of the 5-HT1A receptor.

MAOIs and Meperidine (and other phenylpiperidine opioids)

  • MAOIs: phenelzine (Nardil), isocarboxazid (Marplan), and tranylcypromine (Parnate)
  • Opioids: All phenylpiperidine opioids (meperidine, methadone, tramadol) can react with MAOIs
  • Selegiline: selective MAO-B inhibitor (serotonin is deaminated by MAO-A), relatively safe
  • Symptoms: confusion, fever, diaphoresis, shivering, ataxia, myoclonus, hyperreflexia


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  1. Miller’s Anesthesia, 7th Edition. Page 814
  2. Goodman & Gilman’s, 12th Edition. Chapter 15