Monoamine oxidase inhibitors (also known as MAOIs) are a class of drugs which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression and are particularly effective in treating atypical depression. They are also used in the treatment of Parkinson's disease and several other disorders.
- 1 Mechanism of action
- 2 Poly drug use
- 3 Interactions
- 4 Reduced bio-availability
- 5 List of MAOIs
- 6 See also
- 7 External links
- 8 References
Mechanism of action
MAOIs act by inhibiting the activity of monoamine oxidase, preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B.
MAOA preferentially deaminates norepinephrine (NE), serotonin (5-HT) and epinephrine (E), while MAOB preferentially deaminates benzylamine and phenylethylamine (PEA). Dopamine (DA) and tyramine are equally catabolized by both forms of MAO.
The early MAOIs inhibit monoamine oxidase irreversibly, meaning they permanently deactivate it and the enzyme cannot function until it has been replaced by the body, which can take about two weeks. A few newer MAOIs, known as reversible inhibitors of monoamine oxidase A (RIMAs), are reversible. This means that they are able to detach from the enzyme to facilitate usual catabolism of the substrate.
Poly drug use
Check if your MAOIs also inhibits other substances. Most MAOIs are also cytochrome P450 inhibitors (and tyramine and many other substances are cytochrome P450 substrates) and some are also acetylcholinesterase inhibitors (AChEIs)!
Substances that inhibits the cytochrome P450 system’s ability to metabolize certain drugs, leading to an overall increase in processing times. When the CYP450 system is impacted in this way, it leads to higher levels of certain drugs in your system at one time. This can cause unwanted side effects, and sometimes, an overdose.
Tyramine causes hypertensive crises after MAO inhibition aka the "cheese effect" or "cheese crisis". Using a MAO inhibitor (MAOI), the intake of approximately 10 to 25 mg of tyramine is required for a severe reaction compared to 6 to 10 mg for a mild reaction. Tyramine rich food should also be avoided by people prone to headache and migraine.
Naturally occurring sources with tyramine.
- Psychedelic cacti. The cacti contain contain a bunch of phenethylamines, not just tyramine (but also 3-Methoxytyramine, methyltyramine, hordenine (aka dimethyltyramine), mescaline, etc) and should thus be avoided with MAOIs. However, tyramine has been identified in these species:
|Specie||Tyramine (mg/gram of alive plant)|
|L. williamsii||0.5 - 1|
- Aged cheese (gouda, camembert, cheddar) -- Few cheeses (even. 'mature' cheeses) contain more than 25 mg of tyramine in 100 grams. However, Stilton (a blue cheese) contains up to 217 mg tyramine per 100 grams.
- Aged, smoked or pickled meats
- Aged or fermented soy and yeast products (soy sauce, teriyaki sauce, home baked yeast bread, sourdough bread)
- Overripe fruits
- High amounts of nuts
Candy, and dried fruit:
- Chocolate, especially dark chocolate
- Dried and/or candied fruit rolled in cocoa powder
- Licorice (isoliquiritigenin and liquiritigenin are non-selective MAOIs).
- Licorice candy
- Dried and/or candied fruit rolled in licorice powder
Tyramine formation has been associated with bacterial contamination of foods or temperature abuse conditions, but can also occur as a side effect of generally desired ripening processes. Tyramine is a breakdown product of the amino acid L-tyrosine.
The MAOIs are well-known for their numerous drug interactions, including the following kinds of substances:
- Substances that are metabolized by monoamine oxidase, as they can be boosted by up to several-fold
- Substances that increase serotonin, noradrenaline, or dopamine activity as too much of any of these neurotransmitters can result in severe acute consequences including serotonin syndrome, hypertensive crisis, and psychosis.
- Long-term use with psychoactive substances that interact with MAOIs must be gradually discontinued to avoid discontinuation syndrome. Examples:
- Cannabinoids: Cannabinoids are lipophilic. For example, THC has been detected in heavy cannabis users after 77 days of drug abstinence (Ellis et al., 1985).
- SSRIs: Because of the extended half-life of norfluoxetine, a minimum of 5 weeks should lapse between stopping fluoxetine (20 mg/day) and starting an MAOI. With higher doses the interval should be longer. For example, a serotonin syndrome was reported following a 6-weeks washout in a patient who had been given fluoxetine (80 mg/day).
- Monoaminergics (MA)
- Cholinergics (see also MAOIs that act as acetylcholinesterase inhibitors (AChEIs)), certain substances, examples: alpha-GPC (suspected monoaminergic), centrophenoxine, citicoline (suspected monoaminergic)
- MAOIs, avoid mixing pure MAOIs. Plants with multiple MAOIs like Peganum harmala are fine since they have been evaluated.
- Norepinephrine and dopamine disinhibitors (NDDIs): Fluoxetine
- Neurotransmitter precursors
- Opioids: Some opioid analgesics are associated with a risk of serotonin syndrome in combination with MAOIs due to their serotonergic properties. Other combinations may result in opioid toxicity due to CYP450 enzyme inhibition by the MAOI. Given the widespread availability of several suitable alternative drugs, the combination of dextromethorphan, methadone, pethidine, tramadol, fentanyl or tapentadol with an MAOI should usually be avoided, including in the 14 day period following the withdrawal of an irreversible MAOI. Morphine, codeine, oxycodone and buprenorphine are alternative opioids for patients receiving MAOIs, though starting at a low dose and titrating cautiously against clinical response is advised.
- Racetams: Aniracetam, piracetam
- Receptor agonists
- Releasing agents and monoamine releasing agent (MRA) (or monoamine releaser)
- Dopamine releasing agent (DRA)
- Norepinephrine releasing agent (NRA) (or adrenergic releasing agent), examples: Adrenaline, ephedrine, pseudoephedrine
- Norepinephrine-dopamine releasing agents (NDRAs), examples: Amphetamine, cathinone, phenethylamine, tyramine, methamphetamine
- Serotonin releasing agent (SRA)
- Serotonin–norepinephrine-dopamine releasing agent (SNDRA) (also known as a triple releasing agent (TRA)), examples:
- Reuptake inhibitors and monoamine reuptake inhibitors (MRIs)
- Dopamine reuptake inhibitors (DRI), examples: Armodafinil, ethylphenidate, methylphenidate, modafinil
- Norepinephrine reuptake inhibitor (NRI, NERI) (or adrenergic reuptake inhibitor (ARI)), example: Tapentadol
- Norepinephrine-dopamine reuptake inhibitors (NDRI), examples: Ethylphenidate, methylphenidate, prolintane. Suspected: A-PVP, desoxypipradrol, MDPV
- Serotonin reuptake inhibitor (SRA)
- Serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI), also known as a triple reuptake inhibitor (TRI), examples:
- Serotonin modulator and stimulator (SMS)
- Substituted cathinones, examples: a-PVP, MDPV, methylone, mephedrone
- Substituted phenethylamines
- Substituted tryptamines, examples:
- Tetracyclic antidepressants (TeCA), example: Mirtazapine
- Tricyclic antidepressants (TCA), example: Tianeptine
- Xanthines: Caffeine
- Essential nutrients
- Certain cholinergics (see "Cholinergics")
- Local and general anesthetic
Essential vitamins and minerals
- Vitamin B6: MAOIs may reduce blood levels of vitamin B6.
List of MAOIs
Nonselective MAO-A and MAO-B inhibitors
- Naturally occurring sources
|Natural occuring source||Chemical||MAOI|
|Yangonin (ayahuasca, caapi or yagé)||(−)-epicatechin||MAO-B|
|Banisteriopsis caapi (ayahuasca, caapi or yagé)||(−)-epicatechin||MAO-B|
|Banisteriopsis caapi (ayahuasca, caapi or yagé)||(−)-procyanidins||MAO-B|
|Banisteriopsis caapi (ayahuasca, caapi or yagé)||Harmaline||RIMA|
|Banisteriopsis caapi (ayahuasca, caapi or yagé)||Harmine||MAO-A, MAO-B|
|Black pepper (Piper nigrum)||Piperine||MAO-A, MAO-B|
|Cannabis, Cannabis extract||MAO-A, MAO-B|
|Cocoa bean (from Theobroma cacao)||Caffeine||MAO-A, MAO-B|
|Cocoa bean (from Theobroma cacao)||Catechin||MAO-B|
|Cocoa bean (from Theobroma cacao)||Epicatechin||MAO-B|
|Cocoa bean (from Theobroma cacao)||Tetrahydro-beta-carbolines|
|Coffee (Coffea arabica, Coffea canephora)||Caffeine||MAO-A, MAO-B|
|Coffee (Coffea arabica, Coffea canephora)||Harman||MAO-A|
|Coffee (Coffea arabica, Coffea canephora)||Norharman||MAO-A|
|Liquorice/licorice (Glycyrrhiza Glabra)||Isoliquiritigenin||MAO-A, MAO-B|
|Liquorice/licorice (Glycyrrhiza Glabra)||Liquiritigenin||MAO-A, MAO-B|
|Long pepper (Piper longum)||Piperine||MAO-A, MAO-B|
|Nutmeg (Myristica fragrans)||Kaempferol||MAO-A|
|Nutmeg (Myristica fragrans)||Myristicin||MAO-A, MAO-B?|
|Nutmeg (Myristica fragrans)||Quercetin||MAO-A|
|Passionflower (Passiflora incarnata), weak MAOI||Apigenin||MAO-A|
|Passionflower (Passiflora incarnata), weak MAOI||Harmine||MAO-A, MAO-B|
|Passionflower (Passiflora incarnata), weak MAOI||Kaempferol||MAO-A|
|Passionflower (Passiflora incarnata), weak MAOI||Quercetin||MAO-A|
|Rhodiola rosea||MAO-A, MAO-B|
|Syrian rue (Peganum harmala)||Desoxypeganine||MAO-A|
|Syrian rue (Peganum harmala)||Harmaline||RIMA|
|Syrian rue (Peganum harmala)||Harman||MAO-A|
|Syrian rue (Peganum harmala)||Harmine||MAO-A, MAO-B|
|Tobacco||1,2,3,4-tetrahydro-b-carboline (THbC)||MAO-A, MAO-B|
- Hydrazine (antidepressant)
- Isocarboxazid (Marplan)
- Nialamide (Niamid)
- Phenelzine (Nardil, Nardelzine)
- Tranylcypromine (Parnate, Jatrosom)
- Hydrazine (antidepressant)
Selective MAO-A inhibitors
- Naturally occurring sources
- Bifemelane (Alnert, Celeport) (available in Japan)
- Isocarboxazid (common brand name Marplan)
- Phenelzine (common brand name Nardil)
- Pirlindole (Pirazidol) (available in Russia)
- Tranylcypromine (common brand name Parnate)
Selective MAO-B inhibitors
- Naturally occurring sources
- Betel nut (Areca catechu): MAO-A inhibitor.
- Kava (Piper methysticum): Yangonin. Kava pyrones: The order of potency was desmethoxyyangonin > (+/-)-methysticin > yangonin > (+/-)-dihydromethysticin > (+/-)- dihydrokavain > (+/-)-kavain.
- Olives (Olea europaea), fresh, olive leaf extract: The selective MAO-B inhibitor hydroxytyrosol.
- Rasagiline (Azilect)
- Selegiline (Deprenyl, Eldepryl, Emsam, Zelapar)
- Safinamide (Xadago)
- Naturally occurring sources
- Monoamine oxidase inhibitor (Wikipedia)
- Monoamine oxidase A (Wikipedia)
- Monoamine oxidase B (Wikipedia)
- MAOIs (Erowid Vault)
- Erowid MAOI Vault : Food & Drug Interactions with MAOIs
- Agents That Are Contraindicated With MAOIs and the Corresponding Adverse Events
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- Crosby, D.M.; McLaughlin, J.L. (Dec 1973). "Cactus Alkaloids. XIX Crystallization of Mescaline HCl and 3-Methoxytyramine HCl from Trichocereus panchanoi" (PDF). Lloydia and the Journal of Natural Products. 36 (4): 416–418. PMID 4773270. Retrieved 13 December 2013.
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- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5125943** Tea (Camellia sinensis), black tea, green tea, white tea, oolong tea: The selective MAO-B inhibitors catechin, and epicatechin /?tool=pmcentrez