Monoamine oxidase inhibitors ( MAOI ) are drug classes that inhibit the activity of one or two monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as powerful anti-depressants, as well as effective therapeutic agents for panic disorder and social phobia. They are very effective in depression that is resistant to treatment and atypical depression. They are also used in the treatment of Parkinson's disease and some other disorders.
Reversible inhibitor monoamine oxidase A ( RIMAs ) is a subgroup of MAOI that selectively and reversibly inhibits MAO-A enzyme. RIMAs are used clinically in the treatment of depression and dysthymia. Because they are safer in a single drug overdose, they do not approach the older and irreversible levels of MAOI monoamines such as phenelzine and tranylcypromine. RIMAs has not gained a large market share in the United States. Because of their reversibility, RIMAs are weaker than MAOIs that can not be altered in raising monoamines that are important in depressive disorders.
New research into the MAOI suggests that many concerns about their harmful dietary side effects stem from misunderstandings and misinformation, and that it is still underutilized despite its demonstrated efficacy. The new study also questioned the validity of the severity of perceived dietary reactions, based on outdated studies. Nevertheless, many psychiatrists still reserve monoamine oxidase inhibitors as the last line of treatment, used only when other classes of antidepressant drugs (eg selective serotonin reuptake inhibitors and tricyclic antidepressants) have failed.
Video Monoamine oxidase inhibitor
Medical use
Newer MAOIs such as selegiline (commonly used in the treatment of Parkinson's disease) and reversible moclobemide MAOI provide a safer alternative and are now sometimes used as first-line therapy.
MAOI has been found to be effective in the treatment of panic disorder with agoraphobia, social phobia, atypical depression or mixed anxiety disorder and depression, bulimia, and post-traumatic stress disorder, as well as personality threshold disorder. MAOI appears to be highly effective in the management of bipolar depression according to recent retrospective analyzes. There have been reports of MAOI's efficacy in obsessive-compulsive disorder (OCD), trichotillomania, dysmorphophobia, and avoidant personality disorder, but these reports are from uncontrolled case reports.
MAOI can also be used in the treatment of Parkinson's disease by targeting MAO-B in particular (because it affects dopaminergic neurons), as well as providing an alternative to migraine prophylaxis. The inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety.
MAOIs appear to be specifically indicated for outpatients with complicated dysthymia by panic disorder or hysteroid dysphoria, which involves repeated episodes of depressed mood in response to feelings of rejection.
Maps Monoamine oxidase inhibitor
Side effects
Hypertension crisis
People who consume MAOI generally need to change their diet to limit or avoid foods and beverages containing tyramine. If large amounts of tyramine are consumed, they may suffer from hypertensive crises, which can be fatal. Examples of foods and drinks with high-potency tyramines include animal hearts and fermented substances, such as alcoholic beverages and old cheeses. Excessive concentrations of tyramine in blood plasma can lead to hypertensive crises by increasing the release of norepinephrine (NE), which causes narrowed blood vessels by activating alpha-1 adrenergic receptors. Normally, MAO-A will destroy the excess NE; when MAO-A is inhibited, however, the NE level is too high, causing a dangerous increase in blood pressure.
RIMAs are removed from MAO-A in the presence of tyramine, rather than inhibiting damage to the liver as did the general MAOI. In addition, MAO-B remains free and continues to metabolize tyramine in the stomach, although this is less significant than liver action. Thus, RIMAs is unlikely to cause a crisis of tyramine-mediated hypertension; In addition, dietary modification is usually unnecessary when taking reversible MAO-A (ie moclobemide) inhibitors or low-dose selective MAO-B inhibitors (eg, 6 mg/24 hour transdermal patch selegiline).
Drug interactions
The most significant risks associated with MAOI use are potential drug interactions with over-the-counter and prescribed drugs, drugs or drugs, and some dietary supplements (eg, St. John's wort, tryptophan). It is important that doctors monitor such combinations to avoid adverse reactions. For this reason, many users carry MAOI cards, which allow emergency medical personnel to know what medications to avoid. (For example, an adrenaline dose should be reduced by 75%, and the duration is extended.)
Tryptophan supplements should not be taken with MAOI as a potentially fatal serotonin syndrome may occur.
MAOI should not be combined with other psychoactive substances (antidepressants, painkillers, stimulants, both legal and illegal etc.) unless under expert care. Certain combinations can cause lethal reactions, common examples include SSRIs, tricyclics, MDMA, meperidine, tramadol, and dextromethorphan. Drugs that affect the release or retrieval of epinephrine, norepinephrine, or dopamine usually need to be administered at a lower dose due to the potentially and prolonged effects produced. MAOI also interacts with tobacco-containing products (eg, cigarettes) and can potentiate the effects of certain compounds in tobacco. This may be reflected in the difficulty of quitting smoking, since tobacco contains a naturally occurring MAOI compound in addition to nicotine.
Although safer than general MAOIs, RIMAs still has significant and potentially serious drug interactions with many common drugs; in particular, they can cause serotonin syndrome or hypertensive crisis when combined with almost all antidepressant drugs or stimulants, general migraine, certain herbs, or even most cold medicines (including decongestants, antihistamines, and cough syrup). Withdrawal
Antidepressants including MAOI have some dependence-producing effects, the most important being the withdrawal syndrome, which may be severe especially if the MAOI is stopped suddenly or too quickly. The potential of producing MAOI or antidepressant dependence is generally not as important as benzodiazepines, however. Withdrawal symptoms can be managed by gradual reduction of dose for several weeks, months or years to minimize or prevent withdrawal symptoms.
MAOI, like any antidepressant, does not change the course of the disorder, so it is possible that the termination can return the patient to a pre-treatment state.
This consideration makes it very difficult to switch patients between MAOI and SSRIs, therefore it is necessary to completely remove the system from one drug before starting another. If a person also reduces the dose gradually, the result is that for weeks a depressed patient has to endure depression without chemical help during drug free intervals. It may be better to risk the interaction effects between two drugs, but it is often not easy for the patient.
Interactions
MAOI is renowned for their drug interactions, including the following types of substances:
- Substances are metabolized by monoamine oxidase, since they can be increased up to several times.
- Substances that increase the activity of serotonin, norepinephrine, or dopamine, because too much of these neurochemical chemicals can result in severe acute consequences, including serotonin syndrome, hypertension crisis, and psychosis.
Such substances which may react with MAOI include:
- Phenethylamines: 2C-B, mescaline, phenethylamine (PEA), etc.
- Amphetamines: amphetamine, MDMA, dextroamphetamine, methamphetamine, DOM, etc.
Tryptamines: DMT (Prevent your body from digesting it, allowing someone to experience the effect by taking it orally by Ayahuasca), psilocin/psilocybin ("Magic Mushrooms"), etc. - Lysergamides: ergolines/LSA, LSD ("Acid"), etc.
- Norepinephrine, and/or dopamine reuptake inhibitors:
- Serotonin-norepinephrine reuptake inhibitor (SNRI): desvenlafaxine, duloxetine, milnacipran, venlafaxine.
- Norepinephrine-dopamine reuptake inhibitors (NDRIs): amineptine, bupropion, methylphenidate, nomifensine.
- Norepinephrine reuptake inhibitors (NRI): atomoxetine, mazindol, reboxetine.
- Tricyclic antidepressants (TCA): amitriptyline, butriptyline, clomipramine, desipramine, dosulepine, doxepin, imipramine, lofepramine, nortriptyline, protriptyline, trimipramine.
- Tetracyclic antidepressants (TeCA): amoxapine, maprotiline.
- Opioid derivatives Phenylpiperidine: meperidine/pethidine, tramadol, methadone, fentanyl, dextropropoxyphene, propoxyphene.
- Other: brompheniramine, chlorpheniramine, cocaine, cyclobenzaprine, dextromethorphan (DXM), ketamine, MDPV, nefazodone, phencyclidine (PCP), pheniramine, sibutramine, trazodone
- Serotonin, norepinephrine, and/or dopamine release: 4-methylaminorex (4-MAR), amphetamine, benzphetamine, cathine, cathinone, diethylcathinone, ephedrine, levmetamfetamine, lisdexamfetamine, MDMA ("Ecstasy"), methamphetamine, pemoline, phendimetrazine , phenethylamine (PEA), phentermine, propylhexedrine, pseudoephedrine, phenylephrine, tyramine.
- Local and general anesthesia in surgery and dentistry, especially those containing epinephrine. There is no universally taught or accepted practice of dentistry and the use of MAOI such as phenelzine, and it is therefore very important to inform all doctors, especially dentists, about the potential effects of MAOI and local anesthesia. In preparation for dental work, withdrawal from phenelzine is particularly recommended; because it takes two weeks, but it is not always a desirable or practical option. Dentists who use local anesthesia are advised to use non-epinephrine anesthesia such as mepivacaine at 3% level. Particular attention should be paid to blood pressure during the procedure, and the level of anesthesia should be regularly and properly terminated, since non-epinephrine anesthesia takes longer to become effective and fade faster. Patients taking phenelzine are advised to inform their psychiatrist before dental treatment.
- Other specific supplements: Hypericum perforatum ("St. John's wort"), inositol, Rhodiola rosea, S-adenosyl-L-methionine (SAMe), L-theanine.
- Antibiotics like Linezolid
- Other monoamine oxidase inhibitors.
Action mechanism
MAOI acts by inhibiting the activity of monoamine oxidase, thereby preventing the breakdown of monoamine neurotransmitters and thus increasing its availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A specifically kills serotonin, melatonin, epinephrine, and norepinephrine. MAO-B tends to degrade phenethylamine and other trace amines; otherwise, MAO-A tends to degrade other trace amines, such as tyramine, whereas dopamine is both degraded by both types.
Reversal
The initial covalent MAOIs are bound to the monoamine oxidase enzyme, thus inhibiting them irreversibly; the bound enzyme can not function and thus the enzyme activity is blocked until the cell creates a new enzyme. The enzyme changes about every two weeks. Some of the newer MAOI, known for being moclobemide, are reversible, meaning that they are able to escape from the enzyme to facilitate the usual catabolism of the substrate. Level of inhibition in this way is regulated by substrate concentration and MAOI.
Harmaline is found in Peganum harmala , Banisteriopsis caapi , and Passiflora incarnata is a reversible inhibitor of monoamine oxidase A (RIMA). Selectivity
In addition to reversibility, MAOIs differ from their selectivity from the subtype of the MAO enzyme. Some MAOI inhibit MAO-A and MAO-B simultaneously, other MAOI have been developed to target one from the other.
MAO-A inhibition reduces the disorders, especially serotonin, norepinephrine, and dopamine; Selective inhibition of MAO-A allows tyramine to be metabolized through MAO-B. Agents that act on serotonin when taken with other serotonin-boosting agents may cause a fatal interaction called serotonin syndrome or with irreversible and non-selective inhibitors (such as the older MAOI), MAO hypertensive crisis as a result of special tyramine food interactions. problem with the older MAOI. Tyramine is broken down by MAO-A and MAO-B, so inhibiting this action can cause excessive buildup, so the diet should be monitored for tyramine intake.
Inhibition of MAO-B reduces the interference especially dopamine and phenethylamine so there are no dietary restrictions associated with this. MAO-B will also metabolize tyramine, since the only difference between dopamine, phenethylamine, and tyramine are the two phenylhydroxyl groups on carbon 3 and 4. 4-OH will not be a steric barrier for MAO-B in tyramine. Two drugs MAO-Bi, selegiline and rasagiline have been approved by the FDA without dietary restriction, except in high-dose treatments, where they lose their selectivity.
History
MAOI was initiated by coincidence finding that iproniazid is a powerful MAO inhibitor (MAOI). Originally intended for the treatment of tuberculosis, in 1952, the antidepressant properties of iproniazid were found when the investigators noted that depressed patients given iproniazid had decreased depression. The subsequent in vitro work leads to discovery that inhibits MAO and ultimately on the theory of monoamine depression. MAOI became widely used as an antidepressant in the early 1950s. The discovery of 2 MAO isoenzymes has led to the development of a selective MAOI that may have a more favorable side-effect profile.
The heyday of the older MAOI was largely between 1957 and 1970. The initial popularity of the 'classic' non-selective irreversible MAO inhibitors began to diminish due to their serious interactions with sympathomimetic drugs and tyramine-containing foods that could cause dangerous hypertension. emergency state. As a result, the use by older MAOI medical practitioners declined. When scientists discovered that there were two different MAO enzymes (MAO-A and MAO-B), they developed a selective compound for MAO-B, (eg, selegiline, used for Parkinson's disease), to reduce serious side effects and interactions. Further increases occur with the development of compounds (moclobemide and toloxatone) which are not only selective but cause reversible MAO-A inhibition and reduction in dietary and drug interactions. Moclobemide, is the first reversible inhibitor MAO-A to enter broad clinical practice.
A transdermal patch form of MAOI selegiline, called Emsam, was approved for use in depression by the Food and Drug Administration in the United States on February 28, 2006.
List of MAO inhibitors
Marketed MAOIs
- MAO-A/MAO-B inhibitors are selective
- Hydrazine (antidepressants)
- Isocarboxazid (Marplan)
- Nialamide (Niamid)
- Phenelzine (Nardil, Nardelzine)
- Hidracarbazine
- Non-hydrazine
- Tranylcypromine (Parnate, Jatrosom)
- Hydrazine (antidepressants)
- Selective MAO-A Inhibitor
- Bifemelane (Alnert, Celeport) (available in Japan)
- Moclobemide (Aurorix, Manerix)
- Pirlindole (Pirazidol) (available in Russian)
- Toloxatone (Humoryl) (available in French)
- Selective MAO-B Inhibitors
- Rasagiline (Azilect)
- Selegiline (Deprenyl, Eldepryl, Emsam, Zelapar)
- Safinamide (Xadago)
Linezolid is an antibiotic drug with weak MAO inhibiting activity.
Methylene blue, an antidote indicated for drug-induced methemoglobinemia, among many other off-label uses, is a very powerful and recoverable MAO inhibitor.
MAOI that has been withdrawn from the market
- MAO-A/MAO-B inhibitors are selective
- Hydrazine
- Benmoxin (Nerusil, Neuralex)
- Iproclozide (Sursum)
- Iproniazid (Marsilid, Iprozid, Ipronid, Rivivol, Propylniazida) (not continued worldwide except France)
- Mebanazine (Actomol)
- Octamoxin (Ximaol, Nimaol)
- Pheniprazine (Catron)
- Phenoxypropazine (Drazine)
- Pivalylbenzhydrazine (Tersavid)
- Safrazine (Safra) (not continued worldwide except Japan)
- Non-hydrazine
- Caroxazone (Surodil, Timostenil)
- Hydrazine
- Selective MAO-A Inhibitor
- Minaprine
List of RIMAs
Drugs marketed
RIMAs that occur naturally in plants
- Curcumin (selectivity for MAO-A is disputed)
- Harmaline
- Harmine
Research compounds
References
Source of the article : Wikipedia
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