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Moclobemide

Moclobemide molecule structureMoclobemide molecule structure
Moclobemide
Aurorix, Manerix, Depnil, Clobemix, AmiraOpen in Piru
Psychoactive Class
Antidepressant
Chemical Class
BenzamideMorpholine derivative

Moclobemide is an antidepressant1 in the benzamide and morpholine derivative classes,2 used to treat depression3 and social anxiety4. It was introduced for medical use in 1989.5 It belongs to the reversible monoamine oxidase inhibitor (MAOI) class6 and is generally better tolerated than tricyclic antidepressants.7 It is also used in pharmaceutical ayahuasca preparations to make DMT orally active and prolong its effects. Moclobemide can increase the risk of serotonin syndrome.

Dosage & Duration

Log in Piru

Dosage

Doses are population estimates that vary widely between individuals.

Threshold~150 mg
Light150 mg
Moderate300 mg
Strong600 mg
Heavy600+ mg

Duration

Onset30-90 minutes
Total2-6 hours

Subjective Effects

Subjective Effects not written up yet

Pharmacology

Pharmacodynamics

Moclobemide selectively and reversibly inhibits MAO-A, reducing the breakdown of serotonin, norepinephrine, and dopamine and increasing their availability within neurons and outside cells. It acts as a slow-binding inhibitor, gradually forming a tighter enzyme complex associated with noncompetitive inhibition, without inhibiting neurotransmitter reuptake. MAO inhibition lasts approximately 8-10 hours, and enzyme activity returns to normal within 24 hours of the last dose; a single dose's broader pharmacodynamic action has been reported to persist for approximately 16 hours. Estimates of enzyme inhibition and measurements of brain MAO-A occupancy differ, while MAO-B inhibition is reported in rats and only to a small degree in humans, where metabolites contribute to platelet MAO-B inhibition. Moclobemide and its N-oxide metabolites account for most MAO-A inhibition in humans.

With prolonged treatment, moclobemide reduces beta-adrenoceptor expression and increases cAMP binding to cAMP-dependent protein kinase. It suppresses the unstimulated release of certain proinflammatory cytokines and promotes anti-inflammatory cytokine release. Neuroprotective effects have been reported in rodent models, including effects against hypoxia or ischemia, and antinociceptive activity has been demonstrated in a single-dose study. Initial administration can transiently increase prolactin,8 and long-term treatment increases testosterone in depressed males; findings concerning cortisol and growth hormone remain conflicting. Its anticholinergic and antihistaminic actions are negligible.

Pharmacokinetics

Moclobemide is rapidly absorbed from the gastrointestinal tract, with absorption exceeding 95%.9 Food slows absorption without reducing the amount absorbed.9 Hepatic first-pass metabolism removes about 44% of an initial dose, giving approximately 56% bioavailability; saturation of this effect increases bioavailability to approximately 90% at steady state. Another reported trajectory is an increase from 60% to 80% or more during the first week, when steady-state concentrations are established. It crosses the blood-brain barrier well, with peak central nervous system concentrations reported about 2 hours after administration. Approximately 50% is bound to plasma proteins, mainly albumin,3 and its volume of distribution is 1-1.5 L/kg. Moclobemide undergoes almost complete hepatic metabolism, principally oxidation, including morpholine N-oxidation and C-oxidation, involving CYP2C19 and CYP2D6. It also inhibits CYP1A2, CYP2C19, and CYP2D6; active metabolites occur only in trace amounts. Elimination is predominantly renal, with less than 1% excreted unchanged and 92% of the metabolized drug excreted within 12 hours. Clearance is 30-78 L/hour, and the general elimination half-life is 1-2 hours, increasing somewhat after repeated dosing and reaching about 4 hours in patients with cirrhosis. Substantially impaired liver function slows metabolism, whereas age and renal function do not affect its pharmacokinetics. In overdose, elimination half-life is prolonged twofold to fourfold. Approximately 0.06% is recovered in breast milk.

Interactions

Dangerous

Highest risk

These combinations are considered extremely harmful and should always be avoided. Reactions to these drugs taken in combination are highly unpredictable and have a potential to cause death.

5-MeO-xxT tryptaminesAmphetaminesAMTCocaineDXMMDMAPCPSSRIsTramadol

Unsafe

Avoid

There is considerable risk of physical harm when taking these combinations, they should be avoided where possible.

AlcoholDiphenhydramineMXE

Caution

Use caution

These combinations are not usually physically harmful, but may produce undesirable effects, such as physical discomfort or overstimulation. Extreme use may cause physical health issues. Synergistic effects may be unpredictable. Care should be taken when choosing to use this combination.

2C-T-x compounds2C-x compoundsDOx compoundsKetamineMescalineNBOMe compoundsOpioids
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Tolerance

Tolerance timelines are rules of thumb, not exact schedules, and vary widely between individuals and use patterns.

Full Tolerance
Tolerance to moclobemide's antidepressant effects does not appear to develop during ongoing treatment, with therapeutic benefits maintained for at least 1 year, although tolerance to these effects has been reported in a small number of users. In rats, tolerance to increased extracellular monoamine levels and reduced monoamine metabolite levels does not appear to develop with chronic use.

Harm Potential

Addiction & Dependence

Physical

Low

Withdrawal symptoms are very rare. One patient experienced relatively mild flu-like symptoms lasting seven days after a rapid reduction of high-dose moclobemide therapy.

Toxicity

Lethal Dosage

Single-agent moclobemide overdoses are usually mild and less toxic than overdoses of tricyclic antidepressants or irreversible, non-selective MAO inhibitors.10 All 18 patients who overdosed during clinical trials recovered fully.11

LD50 Data
SpeciesRouteValue
MouseOral730 mg/kg
RatOral1300 mg/kg
Hepatic

Rats receiving 250 mg/kg moclobemide in an 18-month study had mildly elevated alkaline phosphatase and gamma-glutamyl transferase.

Metabolic

Rats receiving 50 or 250 mg/kg moclobemide in an 18-month study showed slight weight loss.

Cardiovascular

Hypertension has occurred very rarely during moclobemide therapy.

Seizure Risk

Low

Moclobemide is believed to have a small proconvulsant effect, and seizures occur rarely. Convulsions are listed among the signs and symptoms of moclobemide overdosage.12

History & Culture

Discovery and development

Moclobemide was discovered in Switzerland in 1972.2 It was initially investigated as a possible lipid-lowering drug or antibiotic, but screening did not support either application. Early testing for antidepressant activity was also negative, and researchers subsequently…

Legality

By Country

Prescription1
Canada flagCanadaPrescription only

References

Source Pages

  1. DrugBank
  2. DrugBank: Moclobemide clinical trials
  3. DrugBank: Moclobemide efficacy
  4. DrugBank: Moclobemide pharmacology
  5. PsychonautWiki: RIMA
  6. Wikipedia

Citations

  1. Moclobemide. A review of its pharmacological properties and therapeutic use in depressive illness. Drugs (1992). https://doi.org/10.2165/00003495-199243040-000091
  2. Did Serendipity Contribute to the Discovery of New Antidepressant Drugs? Historical Analysis Using Operational Criteria. Alpha Psychiatry (2025). https://doi.org/10.31083/ap40037123
  3. Moclobemide 150 mg film-coated tablet - Summary of Product Characteristics. electronic Medicines Compendium (2023). https://www.medicines.org.uk/emc/product/7295/smpc12
  4. Manerix 150 mg and 300 mg film-coated Tablets: Patient Information Leaflet. electronic medicines compendium (2026). https://www.medicines.org.uk/emc/files/pil.6661.pdf1
  5. Bioavailability of moclobemide from two formulation tablets in healthy humans. Pharmazie (2019). https://doi.org/10.1691/ph.2019.88191
  6. Pre-clinical pharmacology of moclobemide. A review of published studies. The British Journal of Psychiatry. Supplement (1989). https://pubmed.ncbi.nlm.nih.gov/26951311
  7. Tolerability of moclobemide, a new reversible inhibitor of monoamine oxidase-A, compared with other antidepressants and placebo. Acta Psychiatrica Scandinavica. Supplementum (1990). https://doi.org/10.1111/j.1600-0447.1990.tb05320.x1
  8. Biochemistry and pharmacology of reversible inhibitors of MAO-A agents: focus on moclobemide. Journal of Psychiatry & Neuroscience (1993). https://e-lactancia.org/media/papers/MoclobemidaBF-JPsyNeur1993.pdf1
  9. MOCLOBEMIDE Product Monograph. AA Pharma Inc. (2023). https://aapharma.ca/downloads/en/PIL/2021/Moclobemide_PM_EN.pdf1234
  10. Moclobemide: An Update of its Pharmacological Properties and Therapeutic Use. Drugs / Springer Nature (1996). https://doi.org/10.2165/00003495-199652030-000131

Further Reading

  1. Australian Prescriber: Should moclobemide be used with other antidepressants?
  2. Bonnet U. (2003). Moclobemide: therapeutic use and clinical studies. CNS Drug Reviews
  3. Fulton & Benfield (1996). Moclobemide: An update of its pharmacological properties
  4. Lotufo-Neto et al. (1999). Meta-analysis of RIMAs for depression
  5. Mayo Clinic: Moclobemide (Oral Route)
  6. Nair et al. (1993). Biochemistry and pharmacology of reversible MAO-A inhibitors
  7. PsychoTropical: Reversible MAOIs in combination with SSRIs
  8. Versiani et al. (1997). Social phobia: long-term treatment with moclobemide
  9. Versiani et al. (1998). Long-term treatment of social phobia with moclobemide
  10. Pilgrim et al. 2012 - Serotonin toxicity involving MDMA (ecstasy) and moclobemide

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