What are MAO inhibitors used for?
Monoamine oxidase (MAO) inhibitors make up a unique class of antidepressants and antihypertensive medications. Although they are now not typically used to treat high blood pressure with the release of novel drugs that are more effective for blood pressure, MAO inhibitors still play a critical role in treating various psychiatric conditions.
What are MAOIs (monoamine oxidase inhibitors)?
Monoamine oxidase inhibitors ( MAOIs) are a class of drugs that inhibit the activity of one or both 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.
What is the role of Mao in the treatment of anxiety?
MAOA and non-selective MAO inhibitors seem to be particularly valuable in the treatment of phobic anxiety and atypical depressions, such as those involving hysterical traits, hypersomnia, bulimia, tiredness and impression of rejection, for which they are superior to amine-uptake inhibitors 74.
Which low molecular weight materials act as endogenous MAO inhibitors?
Low molecular weight materials that can act as endogenous MAO inhibitors include isoquinolium derivatives, harman, isatin, phosphatidylserine and quinolinic acid. However, the physiological significance of their inhibitory effects remains unclear.
What disorder do MAO inhibitors work on?
Monoamine oxidase inhibitors (MAOIs) are a class of drugs that were developed in the 1950s. They're quite effective in treating depression, panic disorder, and other anxiety disorders.
What are the major toxicities of MAO inhibitors?
Severe signs include severe hyperthermia, seizures, central nervous system (CNS) depression, coma, cardiorespiratory depression, muscle rigidity and myoclonus. Though similar to other hyperthermic toxidromes, there are a few ways in which MAOI toxicity can be distinguished.
Why do people take MAO inhibitors?
Monoamine oxidase inhibitors (MAOIs) are a class of medication used to treat depression. They were introduced in the 1950s as the first drugs for depression. Today, they're less popular than other depression medications, but some people benefit from their use.
What drugs are MAOI inhibitors?
MAOIs are most commonly prescribed for patients with social phobia. They include the agents phenelzine (Nardil), selegiline (Emsam), tranylcypromine (Parnate), and isocarboxazid (Marplan).
Which of the following drug produces significant interaction with monoamine oxidase inhibitor?
What drugs interact with MAOIs? MAO inhibitors should be avoided with other antidepressants such as paroxetine fluoxetine, amitriptyline, nortriptyline, bupropion; pain medications like methadone, tramadol, and meperidine; dextromethorphan, St. Johns Wort, cyclobenzaprine, and mirtazapine.
Are antibiotics MAO inhibitors?
However, their use is on the rise in the treatment of neurodegenerative diseases and they are still used in cases of refractory depression. In addition, some antibiotics (eg, linezolid are MAOIs. Although MAOI ingestion is rare, MAOI overdoses can potentially cause significant morbidity and mortality.
What is MAO in pharmacology?
Monoamine oxidase (MAO) is an enzyme involved in the degradation process for various monoamines released by neurons and glia cells, including DA, serotonin and norepinephrine (NE).
What is the major reason that monoamine oxidase inhibitors MAOIs are rarely used in clinical practice today?
These are generally less utilized in current clinical practice due to their poor side-effect profile and potentially dangerous interactions with other drugs and foods, the latter reflecting the cheese, or tyramine, effect.
Where is monoamine oxidase found?
mitochondriaBoth MAO A and B are located throughout the brain in the outer membrane of mitochondria (Green & Youdim 1975) and are encoded by different genes (Bach et al 1988, Grimsby et al 1991).
When were MAOIs developed?
Monoamine oxidase inhibitors (MAOIs) were first introduced in the 1950s. [1][2] They are a separate class from other antidepressants, treating different forms of depression as well as other nervous system disorders such as panic disorder, social phobia, and depression with atypical features.
Which monoamine oxidase inhibitor is used to treat Parkinson's?
FDA-approved MAO-B inhibitors for Parkinson's include selegiline (Zelapar, EMSAM) and rasagiline (Azilect).
Who discovered MAOIs?
3.4) are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first such enzyme was discovered in 1928 by Mary Bernheim in the liver and was named tyramine oxidase.
What is MAO inhibitor?
Monoamine oxidase (MAO) inhibitors were among the first antidepressants to be discovered and introduced into the clinic. Early forms have almost disappeared from use as a consequence of their side effects, which include the 'cheese reaction' — that is, stimulation of cardiovascular sympathetic nervous system activity due to a build-up of dietary amines.
What is the reaction of MAO?
MAO catalyses the oxidative deamination of a range of monoamines, including 5-hydroxytryptamine (5-HT, or serotonin), histamine and the catecholamines dopamine, noradrenaline and adrenaline 1, 2, 3. The reaction produces hydrogen peroxide, the corresponding aldehyde, and either ammonia (in the case of primary amines) or a substituted amine (from secondary amines). For example, methylamine, rather than ammonia, is produced from adrenaline. Although MAO was suggested to be a metallo-enzyme, containing either iron or copper ions essential for activity, it is now known that this is not the case.
What is the role of the mitochondria in cell death?
Mitochondria are responsible for cell survival and death through the regulation of the B-cell leukaemia/lympho ma 2 (BCL2) family anti-apoptotic (BCL2) and pro-apoptotic (BCL-associated death promoter, BAD and BCL2-associated protein X, BAX) proteins. Rasagiline, selegiline, ladostigil and propargylamine have been shown to induce cell survival in response to serum withdrawal or neurotoxins in neuronal cell cultures (SHSY-5Y and PC-12) through the activation of BCL2 and BCL-X L, and the downregulation of BAD and BAX 141, 162, 174, 175, 187. These propargylamines exert their neuroprotective activity by interacting with the mitochondrial outer membrane 174, 187. The propargylamine moiety in these inhibitors prevents neurotoxin-induced collapse of mitochondrial membrane potential, mitochondrial permeability transition and the opening of the voltage-dependent anion channel, as a consequence of the upregulation of anti-apoptotic BCL2 family proteins, which also leads to disinhibition of proteasome function 175, 187, 191. In addition, these propargylamines prevent the nuclear localization of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in response to neurotoxins and reactive oxygen species (ROS) 137, 191, 192. AIF, apoptosis-inducing factor; PKC MARCKS, myristoylated alanine-rich protein kinase C (PKC) substrate; RACK1, receptor of activated PKC; SOD, superoxide dismutase.
What is Norrie disease?
Norrie disease. A rare genetic disorder characterized by bilateral congenital blindness due to a maldeveloped retina. The Norrie disease gene and MAO genes are tandemly arranged on the human X chromosome, and syndromes resulting from chromosomal deletions in two or three of these genes have been identified.
What is monoamine oxidase inhibitor?
Monoamine oxidase inhibitors were among the first antidepressants to be discovered and have long been used as such. It now seems that many of these agents might have therapeutic value in several common neurodegenerative conditions, independently of their inhibition of monoamine oxidase activity.
Where is MAO found in mammals?
In the rat PNS, histochemical studies have shown that MAO is localized in the endothelial cells of the endoneurial vessels, in Schwann cells and in the unmyelinated axons of some neurons 9.
Is MAO a metalloenzyme?
For example, methylamine, rather than ammonia, is produced from adrenaline. Although MAO was suggested to be a metallo-enzyme, contain ing either iron or copper ions essential for activity, it is now known that this is not the case. Two isoenzymes of MAO (MAOA and MAOB) are present in most mammalian tissues 2, 3.
What is the most significant risk associated with the use of MAOIs?
The most significant risk associated with the use of MAOIs is the potential for drug interactions with over-the-counter, prescription, or illegally obtained medications, and some dietary supplements (e.g., St. John's wort, tryptophan ). It is vital that a doctor supervise such combinations to avoid adverse reactions. For this reason, many users carry an MAOI-card, which lets emergency medical personnel know what drugs to avoid (e.g. adrenaline (epinephrine) dosage should be reduced by 75%, and duration is extended.)
What is a reversible inhibitor of monoamine oxidase A?
Reversible inhibitors of monoamine oxidase A ( RIMAs) are a subclass of MAOIs that selectively and reversibly inhibit the MAO-A enzyme. RIMAs are used clinically in the treatment of depression and dysthymia.
What substances can react with MAOIs?
Such substances that can react with MAOIs include: Phenethylamines: 2C-B, mescaline, phenethylamine (PEA), etc. Amphetamines: amphetamine, MDMA, dextroamphetamine, methamphetamine, DOM, etc. Tryptamines: DMT (MAOIs prevent oxidization of DMT in the digestive tract, which renders it biologically inert.
Why do people carry MAOI cards?
For this reason, many users carry an MAOI-card, which lets emergency medical personnel know what drugs to avoid (e.g. adrenaline (epinephrine) dosage should be reduced by 75%, and duration is extended.)
What is the function of MAOIs?
MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine, and norepinephrine.
How often do MAOIs turn over?
The enzymes turn over approximately every two weeks.
When did MAOIs start to wane?
The older MAOIs' heyday was mostly between the years 1957 and 1970. The initial popularity of the 'classic' non-selective irreversible MAO inhibitors began to wane due to their serious interactions with sympathomimetic drugs and tyramine -containing foods that could lead to dangerous hypertensive emergencies.
What is the primary mechanism of action of MAO inhibitors?
Primary Mechanism of Action. MAO inhibitors inhibit monoamine oxidase, an enzyme in the body responsible for degrading several neurotransmitters or messaging chemicals in the brain, including serotonin, norepinephrine, tyramine, and dopamine. There are two subtypes of the MAO enzyme: MAO-A and MAO-B.
What is the MAO enzyme?
There are two subtypes of the MAO enzyme: MAO-A and MAO-B. MAO-A is responsible for degrading serotonin, norepinephrine, and tyramine. MAO-B is responsible for degrading amine-based chemical messengers. Both MAO subtypes degrade dopamine. [19]
How does MAO work?
Through inhibition of MAO, MAO inhibitors increase concentrations of neurotransmitters or chemical messengers in the brain. At therapeutic doses, MAO inhibitors typically inhibit >50% of the total body’s MAO. [21-22] When MAO inhibitors are stopped, MAO regenerates in the body at a rate of approximately 3% per a day. [23] .
How long does MAO last?
The half-life, or time until half of the drug has been metabolized or excreted, of each of the MAO inhibitors is relatively short: 1 Parnate: 2 hours [30] 2 Nardil: 11.6 hours [31] 3 Marplan: 30 min [32] 4 Selegiline: 1.5 hours [33]
Why did the monoamines cause depression?
Because they were noted to increase neurotransmitter or chemical messenger levels in the brain via inhibition of the MAO enzyme, their discovery led to an idea, ultimately called the monoamine hypothesis of depression, that depression was caused or exacerbated by a depletion of neurotransmitters in the brain. [2]
How long after discontinuing MAO inhibitor should I start TCA?
Thus waiting 2 weeks after discontinuing a MAO inhibitor is recommended to allow for sufficient regeneration of MAO before starting a serotonergic drug such as a selective serotonin reuptake inhibitor (SSRI) or tertiary amine tricyclic antidepressant (TCA).
Is Nardil an inhibitor of MAO?
In addition to irreversible inhibition of the MAO enzyme, some MAO inhibitors possess secondary mechanisms of action. possess additional activities in the body. At higher doses, Parnate and, to a lesser extent, Nardil may act as a direct norepinephrine reuptake inhibitor (NRI) [25].
Medical Uses
Side Effects
- Hypertensive crisis
People taking MAOIs generally need to change their diets to limit or avoid foods and beverages containing tyramine, which is found in products such as cheese, soy sauce, and salami. If large amounts of tyramine are consumed, they may suffer a hypertensive crisis, which can be fatal. Ex… - Drug interactions
The most significant risk associated with the use of MAOIs is the potential for drug interactions with over-the-counter, prescription, or illegally obtained medications, and some dietary supplements (e.g., St. John's wort, tryptophan). It is vital that a doctor supervise such combinati…
Mechanism of Action
- MAOIs act by inhibiting the activity of monoamine oxidase, thus preventing the breakdown of monoamine neurotransmitters and thereby increasing their availability. There are two isoforms of monoamine oxidase, MAO-A and MAO-B. MAO-A preferentially deaminates serotonin, melatonin, epinephrine, and norepinephrine. MAO-B preferentially deaminates phenethylamine and certain …
History
- MAOIs started off due to the serendipitous discovery that iproniazid was a potent MAO inhibitor (MAOI). Originally intended for the treatment of tuberculosis, in 1952, iproniazid's antidepressant properties were discovered when researchers noted that the depressed patients given iproniazid experienced a relief of their depression. Subsequent in vitro work led to the discovery that it inhi…
List of Mao Inhibiting Drugs
- Marketed MAOIs
1. Nonselective MAO-A/MAO-B inhibitors 1.1. Hydrazine (antidepressant) 1.1.1. Isocarboxazid(Marplan) 1.1.2. Hydracarbazine 1.1.3. Phenelzine(Nardil) 1.2. Non-hydrazines 1.2.1. Tranylcypromine(Parnate, Jatrosom) 2. Selective MAO-A inhibitors 2.1. Bifemelane(Alnert… - MAOIs that have been withdrawn from the market
1. Nonselective MAO-A/MAO-B inhibitors 1.1. Hydrazines 1.1.1. Benmoxin(Nerusil, Neuralex) 1.1.2. Iproclozide(Sursum) 1.1.3. Iproniazid(Marsilid, Iprozid, Ipronid, Rivivol, Propilniazida) (discontinued worldwide except for France) 1.1.4. Mebanazine(Actomol) 1.1.5. Nialamide(Niami…