Hordenine – Kodiac biolabs

Plain-language summaryIntrigue 35 / 100

Hordenine (N,N-dimethyl-tyramine) is a phenethylamine alkaloid found in germinating barley and several cacti. It is a weak MAO-B inhibitor and a weak monoamine reuptake inhibitor, and the combination slows the breakdown of dopamine and short-lived trace amines like beta-phenylethylamine (PEA). The supplement use angle is to pair it with PEA, where the MAO-B inhibition extends PEA’s normally minutes-long duration into something noticeable. Plasma half-life is one to two hours. The actual pharmacological effects in humans at supplement doses are modest, and most enthusiasm comes from extrapolation rather than human trials. Botanical MAO-B reference compound. Not stocked by Kodiac. This monograph is provided for research and educational reference.

Intrigue 0–100 blends mechanism novelty, evidence strength, and translational potential. Kodiac editorial, not peer-reviewed.

Our opinion on this compoundEstablished workhorse

22/100

Weak botanical MAO-B inhibitor with a narrow PEA-extension niche and no compelling independent research case

Look, hordenine isn’t a bad compound. It’s just not an interesting one, and those are different problems. N,N-dimethyl-tyramine has been in the literature long enough that its pharmacological ceiling is well-understood, and that ceiling is low. Weak MAO-B inhibition, weak monoamine reuptake inhibition, plasma half-life around 1-2 hours. Nothing there surprises anyone who’s read the trace amine literature from the last two decades.

The mechanism isn’t without logic. MAO-B catabolizes beta-phenylethylamine aggressively, which is why PEA’s endogenous half-life is measured in minutes despite its potent monoaminergic effects. Hordenine slows that degradation, so stacking it with PEA extends PEA’s window of action. That’s the entire scientific case for hordenine as a research-relevant compound, and its essentially a delivery-extension story, not a primary mechanism story. We like that the trace amine/TAAR1 space has gotten serious attention in the last decade, but hordenine isnt the probe you reach for when you want to study it properly.

On differentiation, hordenine loses badly to actual pharmacological MAO-B inhibitors. Selegiline is selective, potent, and has a massive preclinical and clinical literature. Rasagiline similarly. Safinamide adds a sodium channel component that gives it real mechanistic depth. Hordenine against those tools is like using a butter knife for something that needs a scalpel. Its botanical origin is sometimes cited as a feature, and we suppose it is if you’re running naturalistic formulation studies, but that’s a thin reason to prioritize it on a serious bench program.

Evidence quality is limited. Theres reasonable in vitro and rodent preclinical data supporting the MAO-B inhibitory activity, but multi-lab replication is sparse and human-facing data at supplement-relevant doses is essentially observational and anecdotal. The pharmacodynamic effects in humans are described uniformly as modest, which is consistent with the weak binding affinities measured in vitro. No robust phase 1 or 2 clinical work anchors the human translation.

Honestly, the only scenario where hordenine earns a place in an active research program is if the program specifically needs a botanical source of mild MAO-B modulation, or if PEA pharmacokinetics are the direct object of study. Both are narrow. Outside those cases, its a mature, well-understood adjunct compound that doesn’t open new questions, doesnt offer unique probe value, and doesn’t differentiate from better tools. A serious investigator would deprioritize this in favor of almost anything else in the phenethylamine or trace amine space.

Novelty: 22
Mechanism promise: 22
In-category differentiation: 18
Evidence quality: 25
Translational signal: 20
Research bench value: 28

Rationale Hordenine scores low across every axis because it’s a decades-old, well-characterized botanical alkaloid whose pharmacology is unremarkable: weak MAO-B inhibition, weak monoamine reuptake inhibition, modest human effect size at supplement doses, and zero differentiation from superior pharmacological tools in its class. Its only credible research angle is as a botanical adjunct extending PEA’s short half-life, which is a narrow probe application rather than a standalone research program.

Phenethylamine MAO-B inhibitor / mild stimulant

N,N-dimethyl-tyramine; a phenethylamine alkaloid found in barley sprouts; a weak MAO-B inhibitor used as a stimulant adjunct.

Abstract

Hordenine (N,N-dimethyl-tyramine; CAS 539-15-1; molecular formula C10H15NO; molecular weight 165.23) is a phenethylamine alkaloid found in germinating barley (Hordeum vulgare) and several cacti. The compound is a weak monoamine oxidase B inhibitor and a weak monoamine reuptake inhibitor; the combined activity slows the degradation of dopamine and trace amines including beta-phenylethylamine (PEA), prolonging their action. Used as a supplement, particularly in combination with PEA where the MAO-B inhibition extends PEA’s normally minutes-long duration. Plasma half-life is approximately 1 to 2 hours. The pharmacological effects in humans at supplement doses are modest. Used as a botanical MAO-B inhibitor in research and in supplement formulations.

Read the full monograph

The full reference document covers compound identification, discovery and developmental history, mechanism of action, pharmacokinetics, sourcing and quality verification, and a curated reference list. Embedded inline below; download for offline reading.

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FOR RESEARCH USE ONLY. Not for medical, diagnostic, or therapeutic purposes. Not for human consumption. All information is provided for research and educational purposes only.