MAO inhibitors: list of drugs and trade names of monoamine oxidase inhibitors

Monoamine oxidase inhibitors (MAOIs)

- biologically active substances that can inhibit the enzyme monoamine oxidase contained in nerve endings, preventing this enzyme from destroying various monoamines (serotonin, norepinephrine, dopamine, phenylethylamine, tryptamines, octopamine) and thereby promoting an increase in their concentration in the synaptic cleft.

Monoamine oxidase inhibitors include some antidepressants, as well as a number of natural substances.

Content

• 1 Classification of MAOIs 1.1 Non-selective irreversible MAOIs
• 1.2 Reversible selective MAO-A inhibitors
• 1.3 Irreversible selective MAO-B inhibitors

MAOI classification

According to their pharmacological properties, monoamine oxidase inhibitors are divided into reversible and irreversible, selective and non-selective.

Selective MAOIs inhibit primarily one type of MAO, while non-selective MAOIs inhibit both types (MAO-A and MAO-B).

Irreversible MAOIs interact with monoamine oxidase, forming chemical bonds with it. The enzyme then becomes unable to perform its functions and is metabolized, and instead the body synthesizes a new one, which usually takes about two weeks.

Reversible MAOIs bind to the active site of the enzyme and form a relatively stable complex with it. This complex gradually dissociates, releasing the MAOI, which then enters the blood and is excreted from the body, leaving the enzyme intact.

Non-selective irreversible MAOIs

• Iproniazid
• Nialamid
• Isocarboxazid
• Phenelzine
• Tranylcypromine

Monoamine oxidase A
Strictly speaking, it is not entirely correct to classify tranylcypromine into this group, since it is a reversible inhibitor, however, it may take up to 30 days to dissociate its complex with the enzyme and completely eliminate it from the body. In addition, it exhibits some selectivity towards MAO-A.

Currently, non-selective MAO inhibitors are rarely used. This is due to their high toxicity. Unlike most other non-selective MAOIs, iproniazid, which is now widely discontinued due to high hepatotoxicity, is not used at all; In many countries, isocarboxazid has also been discontinued for the same reason.

Isoniazid, an anti-tuberculosis drug, historically the first MAOI, also has clinically significant activity: it was the euphoric effect of isoniazid, observed in tuberculosis patients, that led to the discovery of monoamine oxidase inhibitors. Because of its significant hepatotoxicity and potential to cause pyridoxine-deficiency polyneuropathies, isoniazid has ceased to be used as an MAOI, except for its off-label use at high doses in combination with high doses of a vitamin in countries where other hydrazine MAOIs are not available.

Reversible selective MAO-A inhibitors

• Moclobemide
• Pirlindol (pyrazidol)
• Bethol
• Metrolindole
• Garmaline
• Beta-carboline derivatives

Irreversible selective MAO-B inhibitors

• Selegilin
• Rasagiline
• Pargilin

Monoamine oxidase B
The division into MAO-A and MAO-B is partly arbitrary, since in high doses MAO-B lose selectivity and also begin to block MAO-A, and MAO-A in high doses (exceeding the maximum doses recommended in the instructions) also significantly block MAO -B. The division into irreversible and reversible MAOIs is also somewhat arbitrary: only hydrazine derivatives - nialamide, phenelzine, isocarboxazid, iproniazid - are completely irreversible MAOIs. Tranylcypromine and selegiline are partly reversible: after stopping their use, monoamine oxidase is restored not after 2 weeks, as after stopping taking hydrazine MAOIs, but after 5-7 days.

Selegiline and rasagiline are officially registered in Russia only for the treatment of Parkinson's disease. The antidepressant effect of selegiline in monotherapy is observed only in high doses, when it loses its selective effect. However, as potentiators, selegiline and rasagiline can be used in selective MAO-B dosages, in which they act as dopaminergic agents.

Tranylcypromine and selegiline are slightly metabolized in the body into amphetamine, which is partly due to their strong stimulating activity.

MAOIs are not antidepressants

In addition, there are various drugs that function as monoamine oxidase inhibitors but are used to treat conditions other than depression. Listed below are medications that have MAOI properties but are not prescribed to treat depression.

Hydracarbazine . This is a drug with MAOI properties that is used primarily to lower blood pressure. Not many official studies have been conducted using this drug alone.

Isoniazid (Nidrasid) . It was this drug that prompted researchers to study the biological causes of major depression. It is widely used as a first-line prophylactic and treatment for tuberculosis. In the 1950s, it became widely used to treat tuberculosis, and many people began to notice mood-enhancing side effects. Due to numerous reports of mood elevation, this led researchers to create a new generation of antidepressants - MAOIs (monoamine oxidase inhibitors). []

Linezolid . The drug is used as an antibiotic for infections that cannot be treated with other antibiotics. Used to treat pneumonia, various skin infections and infections of the central nervous system. []

Procarbazine (Matulan) . It is a mild MAOI that is used to treat Hodgkin's lymphoma and various types of brain cancer as an anticancer drug. It has been around since 1969 and belongs to a group of drugs called “alkylating agents.” Due to its mild MAO inhibition, it increases neurotransmitter levels in the brain. []

Rasagiline (Azilect) : The drug is often used in treatment during the onset of Parkinson's disease. It inhibits MAO-B 14 times more than MAO-A. It has neuroprotective effects and was created as a result of the possible neurotoxicity of the drug Selegiline. []

Side effects

Non-selective inhibitors

The main adverse effect is orthostatic hypotension, which occurs in almost all patients taking these drugs, while a hypertensive reaction due to the interaction of MAO inhibitors with foods or drugs that can provoke a hypertensive crisis is rare.

Non-selective MAO inhibitors have a large number of side effects. These include dizziness, headache, urinary retention, constipation, fatigue, dry mouth, blurred vision, skin rashes, anorexia, paresthesia, swelling of the legs, convulsive epileptiform seizures, hepatitis. In addition, due to the pronounced psychostimulating effect, these drugs can cause euphoria, insomnia, tremor, and hypomanic agitation; due to the accumulation of dopamine - delusions, hallucinations and other mental disorders. The development of Korsakov's syndrome is possible. Taking non-selective MAO inhibitors often leads to sexual side effects such as decreased libido, erectile dysfunction, delayed or absent orgasm, delayed or absent ejaculation.

Like other antidepressants, MAOIs may precipitate a manic episode in predisposed patients. MAOIs are more likely to cause manic episodes than some other antidepressants, and for this reason they are not the drugs of choice for the treatment of depressive episodes with preexisting manic episodes.

Iproniazid has a pronounced hepatotoxic effect, which makes it unsuitable for widespread use in psychiatry. Phenelzine is less toxic to the liver than iproniazid, but its common side effects are hypotension and sleep disturbances, and isocarboxazid may be used in cases where patients respond well to phenelzine but suffer from these side effects.

Tranylcypromine differs from other MAOIs in its combination of MAO inhibitory properties and amphetamine-like stimulant effects; this drug is partially metabolized to amphetamine. Some patients become dependent on the stimulant effect of tranylcypromine. Compared to phenelzine, it can more often provoke hypertensive crises, but affects the liver less. For these reasons, tranylcypromine should be prescribed with great caution.

Selective inhibitors

They are used more widely because they have significantly fewer side effects. Possible side effects include mild dry mouth, urinary retention, tachycardia, dyspeptic symptoms; in rare cases, dizziness, headache, anxiety, restlessness, and hand tremors are possible. Allergic skin reactions may also occur.

Monoamine oxidase inhibitors

Home Medical Encyclopedia Medicines Drugs acting primarily on the central nervous system

Monoamine oxidase inhibitors (MAO) are a class of drugs that block the activity of monoamine oxidase (a specific protein found in the tissues of the body, in particular the brain, which acts as an “accelerator” of specific chemical reactions), as a result of which norepinephrine accumulates in the brain tissue in significant quantities and serotonin - biologically active substances necessary to normalize the function of the central nervous system.

BEFOL (Befolum)

Pharmachologic effect. Befol is an antidepressant - an MAO inhibitor (monoamine oxidase).

Like other antidepressants of this type of action, it increases the content of neurotransmitter monoamines in the central nervous system, has an antireserpine effect, and potentiates (strengthens) the effect of phenamine.

Indications for use. Prescribed to adults for depression (depression) of various etiologies (causes): endogenous depression in manic-depressive psychosis and various forms of schizophrenia; senile and involutional depressions; reactive and neurotic depression, etc.; depression in patients with chronic alcoholism. Befol is used for mild depression with neurosis-like and not pronounced hypochondriacal symptoms (depressed state caused by fear for health).

Method of administration and dose. Prescribed orally (after meals), intravenously (drip or stream) or intramuscularly. Take 30-50 mg orally (up to 100-150 mg) 2 times a day. Daily dose - up to 400 mg. To avoid sleep disturbance, the second dose of the drug should be no later than 18 hours. For prolonged and resistant (resistant) depression, treatment begins with intravenous administration of the drug by drip (40-60 drops per minute) or stream (within 1-2 minutes). For drip administration, the daily dose of befol is dissolved in 250-500 ml of isotonic sodium chloride solution or 5% glucose solution. Treatment begins with 50 mg, and then the dose is increased to 200-250 mg. When administering befol intramuscularly, single doses can be 10-25 mg, daily doses can be 20-50 mg.

Side effect. The use of befol can cause a decrease in blood pressure, headaches, and a feeling of heaviness in the head. In this case, it is recommended to reduce the dose of the drug. There may also be increased anxiety and irritability. To prevent these phenomena or eliminate them, befol should be combined with antipsychotics and tranquilizers.

Contraindications. Befol is contraindicated in acute inflammatory diseases of the kidneys, liver, poisoning with narcotic, hypnotics and analgesics, as well as during acute alcohol withdrawal (a condition resulting from a sudden cessation of alcohol intake).

Release form. Tablets of 10 mg (0.01 g) and 25 mg (0.025 g) in a package of 50 pieces; 0.25% solution in ampoules of 2 ml.

Storage conditions. List B. In a place protected from light.

INKAZAN (Incazanum)

Synonyms: Metralindole hydrochloride, Metralindole.

Pharmachologic effect. Antidepressant. The psychotropic activity of incasan includes a thymoleptic (mood-improving) effect in combination with a stimulant component. The drug inhibits the reuptake of monoamines. It has no anticholinergic effect.

Indications for use. Depression (state of depression) of various origins (causes): schizophrenia, manic-depressive psychosis, vascular diseases of the brain, etc. Sluggish,. adynamic depression with lethargy, shallow depression with neurosis-like and mild hypochondriacal symptoms (depressed state caused by fear for health).

Method of administration and dose. Orally, starting with 0.025-0.05 g 1-2 times a day, then increasing the dose to 0.05-0.25 g/day. every 2-3 days until a therapeutic effect is achieved. The average daily dose is 0.1-0.2 g. The last dose of incasan to avoid sleep disturbances should be no later than 17 hours.

For prolonged and treatment-resistant (resistant) depression, administer intravenously (40 mg - night sleep disturbances; if necessary, the dose is gradually increased by 25-50 mg per day to 200-350 mg per day (in resistant / difficult to treat / cases, sometimes up to 800 mg).

The therapeutic effect of treatment with nialamide usually appears after 7-14 days. The duration of the course of treatment is individual (from 1 to 6 months). After the onset of the therapeutic effect, the dose of the drug is gradually reduced.

In neurological practice, nialamide is sometimes prescribed for the treatment of neuralgia (inflammation) of the trigeminal (facial) nerve and other pain syndromes.

There are indications that nialamide (0.025 g 2-3 times a day) reduces the frequency and intensity of angina attacks.

Data on the effectiveness of nialamide in the complex therapy of chronic alcoholism have been published. The use of the drug (from 50 to 200 mg per day) improved the general condition and cognitive (cognitive) functions.

Side effect. Nialamid is relatively well tolerated. In some cases, dyspepsia (indigestion), decreased systolic (“upper”) pressure, anxiety, insomnia, headache, dry mouth, stool retention and other side effects are observed.

When prescribing nialamide, it is necessary, however, to take into account the possibility of side effects associated with MAO inhibition. Thus, after using nialamide (and simultaneously with it), imipramine and other tricyclic antidepressants, as well as MAO inhibitors, should not be prescribed; a 2-3 week break is required.

Contraindications. The drug is contraindicated in patients with impaired liver and kidney function, cardiac decompensation, and cerebrovascular accidents (due to the possibility of orthostatic hypotension (a sharp drop in blood pressure when moving from a horizontal to a vertical position). Nialamid should not be prescribed to patients with agitated (excited) conditions.

To avoid the development of “cheese” (tyramine) syndrome, during treatment with nialamide it is necessary to exclude from the diet foods containing tyramine and other vasoconstrictor monoamines (phenylethylamine, etc.), including cheese, cream, coffee, beer, wine, smoked meats.

Nialamid should not be prescribed simultaneously with reserpine and raunatin, as sudden agitation is possible.

To avoid disruption of night sleep, it is not recommended to use nialamide in the evening.

It should be borne in mind that, like other MAO inhibitors, nialamide potentiates (strengthens) the effect of barbiturates, narcotic analgesics (painkillers), local anesthetics, antihypertensives (lowering blood pressure) and other drugs, so combined use should be done with caution if necessary.

Release form. Tablets (dragées) 0.025 g (25 mg).

Storage conditions. List B. In a dry, cool place, protected from light.

PIRAZIDOL (Pirazidolum)

Synonyms: Pirlindol hydrochloride, Pirlindol.

Pharmachologic effect. An antidepressant with a broad therapeutic effect.

Indications for use. Manic-depressive psychoses (psychoses characterized by alternating stages of excited and depressed states), schizophrenia with affective disorders, depressive (depressed) states caused by mental disorders, occurring with psychomotor retardation and an anxious-depressive and anxious-delusional component, anesthetic (loss of emotional reaction on the surrounding reality), hypochondriacal (depressed state caused by fear for health) and neurosis-like symptoms.

Method of administration and dose. Orally, starting from 50-75 mg per day (in 2 doses), with a gradual increase in dose by 25-50 mg. The maximum therapeutic effect is observed at doses of 150-300 mg; if necessary, the dose is increased to 400 mg.

Additional action. With increased sensitivity, dry mouth, sweating, dizziness, tachycardia (rapid heartbeat), fluctuations in blood pressure, sleep disturbances, muscle weakness, dysuric phenomena (impaired urination), which quickly disappear when the dose is reduced.

Contraindications. Acute inflammatory liver diseases, blood diseases, poisoning with drugs, sleeping pills and analgesics. The drug should not be used simultaneously with antidepressants-monoamine oxidase inhibitors, or within 2 weeks. after their cancellation.

Release form. Tablets of 0.025 g and 0.05 g in a package of 50 pieces.

Storage conditions. List B. In a place protected from light.

Sidnophenum

Synonyms: Feprosidnine hydrochloride.

Pharmachologic effect. Sidnofen has a stimulating effect on the central nervous system, but is inferior in this to Sidnocarb and at the same time has pronounced antidepressant activity, which makes it a very valuable drug for the treatment of asthenodepressive conditions (weakness, depression).

The antidepressant effect of sidnofen can be explained by its ability to have a reversible inhibitory (suppressive) effect on the activity of MAO (monoamine oxidase). It reduces the effects of reserpine, enhances the effect of adrenaline and norepinephrine, and causes a moderate increase in blood pressure. Has anticholinergic activity.

Indications for use. Used for asthenic conditions (weakness), of various origins, for adynamia (sharp decrease in range of movements), lethargy, depression, apathy (indifference) due to neuroses, after suffering neuroinfections (infectious diseases of the central nervous system) and for diseases of the endocrine glands, with narcolepsy (a disease of the nervous system), pathological fatigue, as well as simple depression (depressed state), depression with lethargy as part of cyclothymia (mental disorder) and other indications for the use of stimulants and “mild” antidepressants.

Method of administration and dose. Prescribed orally before meals, starting with 0.005 g (5 mg) 1-2 times a day; if necessary, increase the dose by adding 5 mg per day every 2-3 days, up to 0.02-0.03 g per day. Once the therapeutic effect is achieved, the dose is gradually reduced. The maintenance dose (if long-term treatment is necessary) is usually 0.005 g per day.

In severe asthenic conditions, the dose of sydnofen can be gradually increased to 0.06-0.08 g (in a hospital setting).

Take sidnofen in the first half of the day.

Side effect. When using the drug, increased blood pressure, headache, dry mouth, pain in the heart, and rarely allergic itching are possible. In these cases, it is necessary to reduce the dose or take a break from taking the drug.

In rare cases, a “paradoxical” reaction may occur—sedation (a calming effect on the central nervous system).

Contraindications. Sidnofen is contraindicated in patients with anxiety and depression (possible increased anxiety, exacerbation of hallucinatory-delusional syndrome). Sidnofen should not be used simultaneously with antidepressants-MAO inhibitors and tricyclic antidepressants. Between the use of sydnofen and antidepressants of these groups, as well as between antidepressants and sydnofen, a break of at least a week should be observed.

Release form. Tablets 0.005 g (5 mg).

Storage conditions. List A. In a place protected from light.

TETRINDOL (Tetrindolum)

Pharmachologic effect. Its action is similar to pyrazidol, it is a reversible short-acting selective inhibitor of MAO (monoamine oxidase). The drug actively inhibits the deamination of norepinephrine and serotonin and, to a lesser extent, tyramine, which virtually eliminates the risk of developing “cheese” (tyramine) syndrome. An important feature of the therapeutic effect of tetrindole is the rapid onset of the effect. Unlike other antidepressants, the effect of which appears after 7-10 days or later, the effect of tetrindole is observed after 2-3 days from the start of treatment.

Indications for use. The drug is prescribed for depression (state of depression) of various origins: psychogenic (reactive, neurotic); depression caused by organic brain lesions; for depressive disorders in patients with chronic alcoholism.

The use of tetrindole is preferable for depressive states of the cyclothymic level (simple melancholic syndrome, asthenic and dynamic disorders, depression with ideational and motor retardation, depressive disorders with predominantly hypochondriacal symptoms).

In the alcoholism clinic, tetrindole is taken for asthenodepressive states (weakness, depression), dynamic subdepressions occurring with low mood, depression, apathy, increased fatigue in the absence of severe anxiety, insomnia, dysphoric disorders (mood disorders with a predominance of melancholy-angry, gloomy-dissatisfied , combined with irritability, aggressiveness, and often fear), outside the period of acute abstinence (a condition that occurs as a result of a sudden cessation of alcohol intake).

The lack of anticholinergic properties makes it possible to prescribe tetrindole for concomitant glaucoma (increased intraocular pressure), prostate adenoma (benign tumor) and other diseases in which tricyclic antidepressants (amitriptyline), which have an anticholinergic effect, are contraindicated.

Method of administration and dose. Prescribed orally in the form of tablets, starting with a dose of 0.025-0.05 g (25-50 mg) per dose, 2 times a day (morning and evening) with a gradual (over 1-2 weeks) dose increase individually depending on the effectiveness and tolerability up to 0.2-0.4 g (200-400 mg) per day. The selection of optimal doses and duration of treatment depend on the nature and course of the disease, the effectiveness and tolerability of the drug.

Side effect. Tetrindole is usually well tolerated, including in elderly patients. In some cases, exacerbation of anxiety, dry mouth, and headache are possible. When taking the drug in the evening, sleep disturbance may occur.

Contraindications. Inflammatory diseases of the kidneys and liver during exacerbation, as well as during acute alcohol withdrawal.

Release form. Tablets of 0.025 and 0.05 g (25 and 50 mg), film-coated, in glass jars of 50 pieces.

Storage conditions. List B. In a dry place, protected from light.

Interactions

The combination of monoamine oxidase inhibitors with substances that affect monoamine metabolism can lead to an unpredictable increase in their effect and be life-threatening.

Foods incompatible with MAOIs

Significant danger when using MAOIs, especially non-selective irreversible MAOIs

, represents the consumption of foods containing various monoamines and their metabolic precursors. First of all, it is tyramine and its metabolic precursor, the amino acid tyrosine, as well as tryptophan. Tyramine, like amphetamine psychostimulants, causes the release of catecholamines from nerve endings. Its combined use with MAOIs is fraught with a hypertensive crisis (see tyramine syndrome).

Tryptophan is used by the body to produce serotonin, and eating foods containing high amounts of tryptophan can result in serotonin syndrome.

Foods to avoid:

• All cheeses, except fresh homemade cheese (cottage cheese), are especially sharp and aged; milk, cream, sour cream, kefir
• Ice cream with syrup
• Red wine, beer containing yeast (unrefined), Riesling and sherry wines, ale, liqueurs, whiskey
• Smoked meats, salami, chicken and beef liver, chicken pate, meat broths, marinades, any stale meat products, fried poultry and fried game
• Caviar, smoked fish, herring (dried or salted), dried fish, shrimp paste, marinated fish (fresh fish is relatively safe)
• Eggs
• Yeast extracts and brewer's yeast (regular baker's yeast is safe)
• Protein supplements
• Legumes (beans, lentils, beans, soybeans), soy juice
• Sauerkraut
• Overripe fruits, canned figs, bananas, pineapples, avocados, raisins
• Spices
• All types of cookies

Products to be treated with caution:

• White wine, port
• Strong alcoholic drinks (risk of respiratory depression)
• Some fruits such as figs, prunes, raspberries, pineapple, coconut
• Fermented milk products (yogurt, yoghurt, etc.)
• Chocolate
• Soy sauce
• Peanut
• Caffeine, theobromine, theophylline (coffee, tea, mate, Coca-Cola)
• Spinach

Irreversible, non-selective MAOIs require avoidance of these products and the medications and drugs mentioned below while taking them and for two weeks after you stop taking them. In the case of reversible MAOIs, dietary restrictions are usually less stringent and apply to the time the substance remains in the body (no more than a day). You should also refrain from using drugs and surfactants listed in the list together with reversible MAOIs until they are completely eliminated.

Interaction with drugs and narcotics

To prevent tyramine syndrome and serotonin syndrome, the following drugs should be avoided during MAOI therapy:

• Psychostimulants of the amphetamine group and related ones - increasing the levels of catecholamines in the synaptic cleft (amphetamine, methamphetamine, sydnocarb, etc.)
• Any empathogens (entactogens)
• Cold remedies containing sympathomimetics (ephedrine, pseudoephedrine, phenylpropanolamine, phenylephrine, chlorpheniramine, oxymetazoline, etc.): Coldrex, Theraflu, Rinza, etc., nasal sprays and drops (naphthyzine, etc.)
• Weight loss products
• Oral hypoglycemic agents
• Neuronal monoamine reuptake inhibitors: Cocaine
• Cyclic antidepressants, including clomipramine, imipramine
• Selective serotonin reuptake inhibitors (SSRIs), eg paroxetine, citalopram, fluoxetine
• Venlafaxine
• Trazodone, nefazodone

After discontinuation of fluoxetine, a period of at least five weeks should be maintained before initiating an irreversible MAOI to prevent serotonin syndrome. In older patients, this period should be at least eight weeks. After stopping short-acting SSRIs, there should be a break of at least two weeks before prescribing an MAOI.

When switching from irreversible MAOIs to SSRIs, a break of four weeks should be maintained; When switching from moclobemide to SSRIs, 24 hours is sufficient.

The likelihood of developing serotonin syndrome when an SSRI interacts with selegiline or moclobemide is significantly lower compared to the risk of its occurrence when combining an SSRI with a non-selective irreversible MAOI, but such an interaction is still possible. Serotonin syndrome was also observed during monotherapy with moclobemide.

MAOIs potentiate the effect of antipsychotic drugs. The combination of MAOIs with a number of antipsychotics (aminazine, tizercin, teraligen, mazeptil, triftazine, moditene, neuleptil, thioridazine, etc.) can lead to increased toxicity of antipsychotics.

MAO inhibitors potentiate the effect of psychostimulants.

When MAOIs are combined with M-anticholinergics, the anticholinergic effect of M-anticholinergics may be enhanced.

Combination with antiepileptic drugs can lead to a change in the nature of epileptic seizures.

Irreversible MAOIs should not be combined with antihypertensive drugs due to the risk of severe orthostatic hypotension, or the dose of the antihypertensive drug should be reduced.

When used in combination with ganglion blockers, the effect of ganglion blockers is enhanced; this combination should be used with caution, starting treatment with small doses.

In combination with alpha-agonists, the risk of arrhythmias increases; the use of this combination is unacceptable. The risk of arrhythmias also increases when used together with beta blockers.

MAOIs enhance the effect of alcohol, sedatives and anxiolytics, as well as painkillers, sometimes bringing the effect of these drugs beyond the safety line.

MAOIs can complicate procedures involving anesthesia or analgesia, as they interact with narcotic substances, causing a syndrome manifested by agitation, fever, headaches, convulsions, coma with the possibility of death. They can cause respiratory depression. Fatal outcomes have been reported with the use of meperidine. Patients undergoing surgery should have their dose of MAO inhibitors reduced in advance to avoid adverse drug reactions.

The combined use of MAOIs and procarbazine may cause fever, seizures, and death.

MAOIs may enhance the hepatotoxic effect of hormonal contraceptives.

Diabetic patients taking insulin may experience a more dramatic decrease in blood sugar levels. In this case, the insulin dose can be reduced. The hypoglycemic effect of oral hypoglycemic drugs may also be enhanced.

The combined use of MAOIs and drugs for iodine therapy increases the side effects of MAOIs, so the use of this combination is unacceptable.

A MAO inhibitor should not be prescribed in combination with an MAO inhibitor: this can lead to fever, convulsions, and death (after stopping one MAO inhibitor, an interval of at least two weeks should be maintained before prescribing another MAOI).

Non-medical use

There are a number of reports of abuse of MAO inhibitors. The mechanism of abuse may be due to the similarity of the chemical structure of MAOIs to the chemical structure of amphetamine; however, the mechanism of action of MAOIs and amphetamines differs significantly. Individuals who abuse MAOIs may be particularly prone to developing hypertensive crises because they use high doses of MAOIs and/or may be unaware of the recommended diet.

Interactions with phenylethylamine and tryptamine psychedelics

Most tryptamines are good substrates for MAO-A. DMT and 5-MeO-DMT, when taken orally, are metabolized by it in the gastrointestinal tract and liver, without having time to enter the blood, so they are inactive when taken orally. 4-Hydroxy-DMT (psilocin) is less susceptible to degradation by MAO because its hydroxyl group at the 4th position makes it difficult to bind to the active site of the enzyme, making it orally active. Alkyl substituents on the amino group, more voluminous than methyl (ethyl, propyl, cyclopropyl, isopropyl, allyl, etc.), also complicate the metabolism of tryptamines with such substituents through MAO, therefore all such tryptamines are active when taken orally. The alpha-methyl in tryptamine molecules like AMT and 5-MeO-AMT significantly impedes their metabolism by MAO and turns them de facto from substrates into weak inhibitors of this enzyme.

Inhibition of peripheral MAO-A in the GI tract and liver by potent MAOIs allows tryptamines such as DMT and 5-MeO-DMT to be orally active and also enhances and prolongs the effects of other tryptamines such as psilocin and DET. On the other hand, long-term use of MAOIs as antidepressants significantly reduces the effects of psychedelics. This occurs, obviously, due to changes in the monoaminergic systems of the brain caused by increased levels of monoamines. The nature of this phenomenon currently remains unclear and is not explained by a simple loss of sensitivity of the serotonin receptors with which psychedelics interact.

Thus, taking MAOIs together with tryptamines or immediately before using tryptamines prolongs and in some cases enhances the effects of the latter, and in addition makes it possible to use tryptamines such as DMT orally. This is the basis of the principle of action of ayahuasca and similar mixtures, including the so-called pharmacohoasca, in which pure DMT is used instead of plant components, and traditional Banisteriopsis Caapi, and Peganum Harmala seeds, or their extracts, or even moclobemide (Aurorix). However, taking an irreversible MAOI a few days before taking a psychedelic will weaken its effects. The same thing will happen with long-term use of both irreversible and reversible MAOIs before taking a psychedelic drug.

Taking 5-MeO-DMT with an MAOI is not safe. Many people note strong and unpleasant side effects of this combination, including serotonin syndrome. In addition, many people find this experience extremely difficult psychologically and can be associated with serious mental health risks.

Tryptamines, which significantly increase monoamine levels in the synaptic cleft (AMT, 5-MeO-AMT, AET, etc.), can be lethal when combined with MAOIs. There is some concern about the safety of using MAOIs with tryptamines such as DPT.

The metabolism of LSD is currently not well understood, but MAO does not appear to be involved in any way. However, according to some authors, when used in conjunction with harmala, its effects are enhanced and prolonged. The same applies to other ergolines.

MAO plays a minor role or even practically does not participate in the metabolism of phenylethylamine psychedelics. Therefore, taking MAOIs together with them is devoid of practical meaning. Although, according to some users, both harmala and moclobemide enhance the effects of some PEAs, such as 2C-B.

In most cases, taking MAOIs with phenylethylamine psychedelics does not pose a serious health risk. However, the use of MAOIs with sulfur-containing phenylethylamines such as 2C-T-7 and Aleph-7 should be avoided due to their controversial and poorly studied effects on brain monoamine levels and high toxicity. Combinations of MAOIs with TMA-6 and TMA-2 may also be unsafe.

What are MAO inhibitors?

MAO inhibitors (MAOIs) are one of the oldest types of antidepressant drugs. Their mechanism of action is based on the blockade of monoamine oxidase, a protein enzyme that destroys monoamines. How can this circumstance be related to the treatment of depression? Everything is very simple - after all, monoamines include many substances that are commonly called neurotransmitters - serotonin, dopamine, norepinephrine. It is their lack in the body (more precisely, in the nerve circuits) that causes a depressed mood, a state of depression. MAOIs destroy monoamine oxidase or temporarily block its action, resulting in increased levels of neurotransmitters in neural circuits. The brain begins to work more efficiently, and this affects a person’s mood - he gets rid of depression, despondency and apathy.

The effect of MAO inhibitors occurs when the enzyme activity decreases by approximately 2 times.

Overdose

MAOI antidepressants are extremely toxic in overdose, and symptoms of intoxication do not necessarily appear immediately. In acute poisoning with large doses of MAOIs, general weakness, dizziness, ataxia, slurred speech, and clonic muscle twitching are observed; this is followed by the development of comatose states or convulsive seizures (such as generalized epileptiform seizures) followed by coma. After emerging from a coma, the stunned state may persist for some time. In some cases, coma does not occur, and the initial symptoms of overdose are replaced by delirious syndrome. Impaired consciousness in case of MAOI overdose is not always observed; in cases where they are absent, the depression that caused the prescription of MAOIs very quickly, paroxysmally, gives way to euphoria.

Manifestations of overdose may also include anxiety, confusion, hypertensive crisis, cardiac arrhythmias, rhabdomyolysis, and coagulopathies.

Due to the high toxicity of MAOIs, they should be prescribed to patients with suicidal tendencies in quantities sufficient for only a few days of use.