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Phenylethylidenehydrazine (PEH) is a metabolite of the antidepressant phenelzine and a research compound in its own right. Its main action is inhibition of GABA-transaminase (GABA-T), the enzyme that breaks down GABA, so it raises brain GABA levels; this GABA-boosting effect is thought to account for much of phenelzine's distinctive anti-anxiety character. It also influences phenylethylamine (PEA) metabolism. PEH is not a medicine you can be prescribed; it is studied mainly to tease apart which of phenelzine's effects come from raising GABA versus inhibiting monoamine oxidase.
- Raises brain GABA via GABA-T inhibition
- Thought to explain much of phenelzine's anti-anxiety effect
- Useful research tool for separating GABAergic from MAO-inhibiting effects
- Possible anticonvulsant and neuroprotective actions under study
- Retains some MAO inhibition, so MAOI-style interaction risks apply
- Potential tyramine dietary reaction
- Serotonin syndrome risk if combined with serotonergic drugs
Mechanism
PEH is formed when the body metabolizes phenelzine, and it is a potent inhibitor of -transaminase (GABA-T), the enzyme that normally degrades the inhibitory neurotransmitter GABA. By blocking that breakdown, PEH raises brain GABA levels, producing a calming, anti-anxiety, and potentially anticonvulsant and neuroprotective effect; researchers believe this action explains a large share of phenelzine's anti-anxiety benefit, separate from its monoamine oxidase inhibition. Compared with its parent, PEH is a much weaker inhibitor of monoamine oxidase, which makes it a useful tool for separating the GABA-raising effects from the MAO-inhibiting effects that phenelzine bundles together. It also affects the metabolism of phenylethylamine (PEA), a natural trace amine. PEH remains an investigational research compound rather than an approved drug.
receptor fingerprint
-transaminase (GABA-T)Inhibitor
Phenylethylamine (PEA) metabolismModulates
Monoamine oxidase (MAO)Weak inhibitor
Safetyrisks and cautions, not medical advice
PEH is a research compound, not an approved or prescribable medicine, so there is no established human safety profile and no clinical dosing; almost everything known about it comes from laboratory and animal studies. Because it does retain some monoamine oxidase inhibition and shares chemistry with phenelzine, the standard MAOI-style cautions are prudent to assume: the tyramine dietary reaction, where tyramine-rich aged or fermented foods could raise blood pressure, and the serotonin syndrome risk from combining any MAO-inhibiting compound with serotonergic drugs (SSRIs and other antidepressants, certain migraine or pain medicines, MDMA). It should be treated as an experimental substance and not something to self-administer. Not medical advice.
Subjective profileweighing the evidence above
Valuable as a research tool for separating phenelzine's GABA effect from its MAO inhibition, and that is where its usefulness ends. No human safety profile, no dosing, and it retains enough MAO inhibition to carry the tyramine and serotonin risks without any of phenelzine's oversight.
Resources
This entry is here for reference.
Research
- 2002first citedEffects of the antidepressant/antipanic drug phenelzine and its putative metabolite phenylethyl…
- 2008most recentNeurochemical effects of the monoamine oxidase inhibitor phenelzine on brain GABA and alanine:…
- 1.Phenylethylidenehydrazine, a novel GABA-transaminase inhibitor, reduces epileptiform activity in rat hippocampal slices
- 2.Neurochemical effects of the monoamine oxidase inhibitor phenelzine on brain GABA and alanine: A comparison with vigabatrin
- 3.Effects of the antidepressant/antipanic drug phenelzine and its putative metabolite phenylethylidenehydrazine on extracellular gamma-aminobutyric acid levels in the striatum
3 listed here; entry last updated August 2026
Reviews
My notesprivate to this device
FAQ
What is PEH?
Phenylethylidenehydrazine, a metabolite of the MAOI antidepressant phenelzine. It inhibits GABA-transaminase and raises brain GABA, and it is studied as a research compound rather than used as a medicine.
Why do researchers care about PEH?
It lets them separate two of phenelzine's actions. PEH strongly raises GABA but only weakly inhibits monoamine oxidase, so it helps show how much of phenelzine's calming, anti-anxiety effect comes from GABA rather than from MAO inhibition.
Is PEH safe to take?
There is no established human safety data; it is an experimental compound. Because it still inhibits some monoamine oxidase, the MAOI cautions are prudent to assume, including the tyramine dietary reaction and serotonin syndrome risk with serotonergic drugs.
Limitations of the evidence
- Unknown human safety profile; experimental only
Adverse effects
- Retains some MAO inhibition, so MAOI-style interaction risks apply
- Potential tyramine dietary reaction
- Serotonin syndrome risk if combined with serotonergic drugs