Monoamine oxidase inhibitors

A special group is represented by drugs for the treatment of depression, the therapeutic effect of which is associated with inhibition of the activity of the mitochondrial enzyme monoamine oxidase, accompanied by a decrease in the breakdown of catecholamines, as well as indole amines. Most monoamine oxidase inhibitors (MAOIs) act non-selectively and therefore increase the levels of not only catecholamines and serotonin, but also dopamine.

Monoamine oxidase inhibitors (iproniazide), like tricyclic antidepressants, appeared in the 50s of the twentieth century, in the process of searching for drugs needed to treat tuberculosis.

Opinions about the effectiveness of these antidepressants are controversial. In some cases, they are effective for depression resistant to other antidepressants, increased appetite, drowsiness, and atypical course of depression.

The effect of MAOIs on blood pressure is unpredictable, since these drugs increase the level of norepinephrine and adrenaline in the blood, the blood pressure numbers increase. At the same time, MAOIs inhibit the vasomotor centers and thereby reduce sympathetic activity (Anthony P., et al., 2002). The first signs of increased blood pressure may be pain in the occipital region, heaviness in the heart, intense pulse, and fainting.

In order to prevent a sharp increase in blood pressure while taking these drugs, you should exclude certain medications (desensitizing agents, anesthetics and painkillers), as well as foods containing tyramine (cheese, pizza, sour cream, smoked beef, sauerkraut, legumes , avocado, yeast products, soy sauce, etc.), drinks (champagne, beer, whiskey, coffee, chocolate). Normally, tyramine is destroyed by MAOIs before it is absorbed, but under conditions of inhibition of monoamine oxidase activity, tyramine contained in food products is absorbed. Subsequently, it is captured by adrenergic neurons, participates in synthetic processes and turns into a “false transmitter” - octopamine, which in turn leads to a massive release of norepinephrine and can cause a hypertensive crisis (Anthony P., et al., 2002). MAOI drugs are metabolized in the liver and, if this organ is diseased, can cause toxic damage.

According to L. Elkin et al. (1989), non-selective MAO inhibitors are of secondary importance in the treatment of depression and are used only for simple and mild depression and when other, safer methods of treatment do not help. These are old, currently rarely used inhibitors - phenelzine (Nardil), isocarboxazid (Marplan), tranylcypromine (parnate).

The effectiveness of combining MAO inhibitors with TCAs has been shown for depression that is insensitive to the latter drugs (Pande A., et al., 1991). Non-selective MAO inhibitors can also be effective in atypical depression (hyperphagia, hypersomnia, anxiety and phobias) (Puzhinsky S., 2000). MAOIs are considered to be more effective than TCAs in the treatment of atypical depression.

The half-life of MAOIs is approximately 2.5 hours, maximum MAO binding (maximum effectiveness) is observed 14 hours after absorption of MAOIs, however, the antidepressant effect of these drugs does not appear until 4 weeks after the start of therapy.

Modern selective monoamine oxidase inhibitors that inhibit the activity of isolated isoenzyme A or B include: selective monoamine oxidase inhibitors type A - pyrazidol, moclobemide, selective monoamine oxidase inhibitors type B - selegiline (used in the early stages of Parkinson's disease).

MOCLOBEMIDE

Composition and release form

Moclobemide. Tablets (100 mg, 150 mg, 300 mg).

pharmachologic effect

Moclobemide is an antidepressant, a reversible MAO-A inhibitor. Inhibits the metabolism of norepinephrine and serotonin, which leads to an increase in their concentration in the central nervous system. Moclobemide improves mood and psychomotor activity, helps reduce symptoms such as dysphoria, nervous exhaustion, lethargy and decreased ability to concentrate.

These effects of the drug appear in most cases during the 1st week of treatment. Despite the fact that moclobemide does not have sedative properties, it improves the sleep of patients within a few days after the start of treatment. Moclobemide has no effect on the reaction rate.

Indications

Depressive syndromes

Application

Treatment should begin with a daily dose of 0.3 g, usually divided into 3 doses. When a clinical effect is achieved, the dose can be reduced to 0.15 g/day. For severe depression, the dose can be increased to 0.6 g/day if necessary. The dose should be increased no earlier than 1 week after the start of treatment. Moclobemide should be taken at the end of a meal. Elderly patients do not need to adjust the dose of moclobemide.

For patients with impaired liver function, the dose of moclobemide is 1/2-1/3 of the average therapeutic dose. In patients with thyrotoxicosis and pheochromocytoma, the drug should be used with caution (due to the possibility of hypertensive reactions).

For patients in whom agitation is the main clinical manifestation of the disease, moclobemide is not prescribed or is prescribed only in combination with sedatives. When treating patients with schizophrenic or schizoaffective psychoses, schizophrenic symptoms may increase. These patients should, if possible, continue long-term therapy with antipsychotics.

Patients with high blood pressure taking moclobemide should avoid eating large amounts of foods rich in tyramine. Patients taking moclobemide usually do not experience a decrease in the ability to concentrate. However, at an early stage of treatment, the patient's response rate should be monitored.

Pregnancy and lactation

Due to the lack of clinical data on the effect of moclobemide on the fetus, its use during pregnancy and lactation should be avoided.

Side effect

On the central nervous system, psyche: nervousness, sleep disturbances, dizziness, restlessness, anxiety, agitation, blurred vision, in very rare cases - signs of confusion that disappear after discontinuation of the drug. On PS: dry mouth, nausea, feeling of fullness in the stomach, heartburn, diarrhea, constipation.

Contraindications

Hypersensitivity to the drug; acute cases of confusion; childhood.

Overdose

Symptoms Agitation, increased aggressiveness, and disturbances in relationships with other people were observed. Treatment of overdose is symptomatic.

Moclobemide

Alcoholic drinks containing tyramine (beer, ale, wine) sometimes cause a hypertensive reaction.

Antidepressants (fluoxetine, citalopram) - possible development of serotonin syndrome - development of potentially fatal serotonin syndrome.

Dextromethorphan - nausea, tremor, dizziness and vomiting, moderate agitation.

Meperidine and possibly other opioid analgesics - potentiation of their effects. The combined use of meperidine and moclobemide is contraindicated; use other opioid analgesics with caution.

Sympathomimetics, including epinephrine with local anesthetics, cause a sharp increase in systolic pressure. Do not use drugs containing ephedrine, amphetamine or adrenergic agonists.

Altretamine - when administered in combination, severe orthostatic hypotension is possible.

Cimetidine - inhibition of metabolism and increased concentrations and toxicity of moclobemide.

The combination of amitriptyline + chlordiazepoxide is incompatible with MAO inhibitors (due to the risk of developing serotonin syndrome, including myoclonus, agitated spasms, delirium and coma). The use of the combination of amitriptyline + chlordiazepoxide can be started one day after discontinuation of the reversible MAO inhibitor moclobemide. The use of MAO inhibitors can be started 2 weeks after discontinuation of the amitriptyline + chlordiazepoxide combination. In any case, both moclobemide and the combination of amitriptyline + chlordiazepoxide should be started with small doses, gradually increasing them depending on the effect.

An increase in blood pressure and the occurrence of a hypertensive crisis have been described after the simultaneous use of buspirone and moclobemide (a reversible MAO inhibitor); therefore, buspirone cannot be combined with moclobemide. At least 14 days must pass after stopping buspirone before starting moclobemide; however, buspirone can be started 1 day after stopping moclobemide.

Moclobemide inhibits MAO and, against the background of venlafaxine, provokes the development of adverse reactions,

When used simultaneously with zolmitriptan - an increase in the maximum plasma concentration and AUC of zolmitriptan; with clomipramine - cases of serotonin syndrome have been described; with levodopa - possible headache, nausea, insomnia; with selegiline - increased sensitivity to tyramine; with sumatriptan - increasing the bioavailability of sumatriptan; with fluoxetine, citalopram - the development of serotonin syndrome is possible.

Moclobemide enhances the effect of glipizide and diazepam.

Repaglinide - moclobemide inhibits MAO and enhances the hypoglycemic effect.

Moclobemide prolongs and enhances the anticholinergic effect of diphenhydramine.

The systemic effect of ibuprofen can be enhanced and prolonged with simultaneous administration of moclobemide.

Carbamazepine - moclobemide, as an MAO inhibitor, increases the likelihood of side effects.

Carvedilol - enhances the effect on blood pressure (hypotension) and heart rate (bradycardia).

Clonazepam - potentiation of central nervous system depression.

Methyldopa - enhances the antihypertensive effect; at the same time, cases of the development of a hypertensive crisis with psychomotor agitation have been described; co-administration is not recommended.

Metoclopramide - Moclobemide inhibits MAO and increases the duration of circulation of catecholamines released by metoclopramide.

Promethazine - moclobemide increases the risk of developing extrapyramidal disorders (inhibits MAO).

Salmeterol, terbutaline - moclobemide as an MAO inhibitor may enhance the effect on the cardiovascular system.

Moclobemide inhibits MAO and, when combined with sertraline, can lead to severe, life-threatening reactions, including hyperthermia, rigidity, myoclonus, autonomic disturbances, delirium and coma; simultaneous and/or sequential use is contraindicated.

Tramadol - moclobemide inhibits MAO and increases the risk of serotonin syndrome (fever, agitation, trembling and restlessness, seizures).

Moclobemide inhibits MAO, prolongs and enhances the anticholinergic effects of cyproheptadine and CNS depression; combined use is contraindicated.

Moclobemide
International name of the medicinal substance:
Moclobemide The list of drugs containing the active substance Moclobemide is given after the description.
Pharmacological action:
Antidepressant, selectively and reversibly inhibits MAO type A, inhibits the metabolism of serotonin (mainly), norepinephrine and dopamine, increases their content in the central nervous system.
Possessing an antidepressant effect, it improves mood and concentration, eliminates increased fatigue, dysphoria, nervous exhaustion, psychomotor retardation, and improves sleep. The optimal antidepressant effect develops when MAO is suppressed by 60-80%. The effect appears by the end of 1 week of treatment. Does not have a negative effect on the reaction rate. Pharmacokinetics:
Absorption is rapid and complete after oral administration. TCmax - 1 hour after a single dose. Css is created by the end of 1 week of treatment. Bioavailability (depending on the dose taken) is 40-80%. Volume of distribution - 1.2 l/kg. Communication with plasma proteins (albumin) - 80%. Easily passes tissue barriers, apparent volume of distribution is about 1.2 l/kg. Metabolized in the liver during oxidative reactions by isoenzymes CYP2C9 and CYP2D6. In the form of metabolites (1% unchanged) it is quickly excreted by the kidneys, total clearance is 333-833.3 ml/min, T1/2 is 1-4 hours.

Indications:
Depression of various etiologies (with manic-depressive psychosis, various forms of schizophrenia, chronic alcoholism, senile and involutional, reactive and neurotic), social phobia.
Contraindications:
Hypersensitivity;
acute conditions accompanied by “confusion” of consciousness; excitement, agitation, pheochromocytoma, pregnancy, lactation, childhood. With caution. Thyrotoxicosis. Side effects:
From the nervous system: dizziness, headache, anxiety, agitation, agitation, insomnia, fear, blurred vision, paresthesia, rarely - confusion.
From the digestive system: dry mouth, nausea, heartburn, constipation or diarrhea, feeling of heaviness in the stomach. Allergic reactions: skin rash, itching, urticaria. Other: hyperhidrosis. Interaction:
Strengthens and prolongs the effect of adrenergic stimulants, opiates and ibuprofen.
Strengthens the vasoconstrictor effect of tyramine contained in food products, which (if possible) requires its exclusion from the diet. It is not recommended to combine with clomipramine (the likelihood of severe reactions from the central nervous system increases). Treatment with tricyclic and other antidepressants can be started immediately after discontinuation of moclobemide. Does not change the pharmacodynamics and pharmacokinetics of indirect anticoagulants, digoxin and ethanol. Cimetidine and other microsomal oxidation inhibitors slow down metabolism. Dextromethorphan increases the risk of severe central nervous system side effects. Concomitant use of selegiline is contraindicated. Special instructions:
In patients with schizophrenia, it can cause aggravation of the course of the disease (prescription is possible only under the guise of antipsychotic drugs).
Against the background of thyrotoxicosis or pheochromocytoma, as well as in patients with initially elevated blood pressure (especially those receiving large amounts of tyramine from food), a significant increase in blood pressure is possible. Preparations containing the active substance Moclobemide:
Aurorix

The information provided in this section is intended for medical and pharmaceutical professionals and should not be used for self-medication. The information is provided for informational purposes only and cannot be considered official.

Pyrazidol

Pyrazidol is a domestic antidepressant with a balanced action; it selectively inhibits MAO type A (short-term and completely reversible). The thymoanaleptic effect manifests itself in the relief of depressive symptoms, primarily vital melancholy, mental anesthesia and psychomotor retardation.

This drug normalizes the metabolism of monoamine neurotransmitters, blocks the deamination of serotonin, to a lesser extent norepinephrine, and to a small extent tyramine, and partially inhibits the reuptake of monoamines. It exhibits nootropic properties and improves cognitive function. It should be borne in mind that pyrazidol is mainly used for mild depression or its moderate forms, including neurotic and masked depression, and may be ineffective for severe depression accompanied by manifestations of agitation (up to 50% of patients with deep depression of the melancholic type give a positive response to therapy pyrazidol). The drug is also used for Alzheimer's disease, “organic” depression, and alcohol withdrawal syndrome. Pyrazidol is also used in the treatment of psychosomatic disorders, astheno-depressive symptoms that have developed against the background of myocardial infarction and cerebral atherosclerosis (the drug combines well with other medications). The medication has a normalizing effect on the lungs during manifestations of hypoxia.

The therapeutic effect after taking pyrazidol appears 3-5 days after the start of therapy. The optimal daily dose of the drug is 15-300 mg. (begin treatment with 50-75 mg in two doses). When the dosage of the drug is over 200 mg. its sedative effect begins to dominate, and more than 400 mg. the drug may have an effect on severe endogenous depression.

The balanced action of pyrazidol is characterized by a combination of an antidepressant effect with an activating effect in adynamia and apathy and a sedative effect in an agitated state. As a result of the above, the drug is effective for mixed, atypical depression.

During the treatment process, such comorbid symptoms of depression as: manifestations of senesto-hypochondria, obsessive-compulsive disorder, and signs of depersnonalization also disappear.

Side effects of pyrazidol are mild and limited to dry mouth, sweating, weakness, and tachycardia. Allergic reactions and dizziness occur more rarely. Unlike TCAs, the drug does not have an anticholinergic effect. Contraindications to the drug are acute hepatitis and blood diseases.