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 have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression. They are also used in the treatment of Parkinson’s disease and several other disorders.
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, though they have not gained widespread market share in the United States. Because of their reversibility and selectivity, RIMAs are safer than the older MAOIs like phenelzine and tranylcypromine.
Types of Monoamine Oxidase Inhibitor
Marketed MAOIs
Nonselective MAO-A/MAO-B inhibitors
Hydrazine (antidepressant)
- Isocarboxazid
- Nialamide
- Phenelzine
- Hydracarbazine
- Non-hydrazines
- Tranylcypromine
Selective MAO-A inhibitors
- Bifemelane
- Moclobemide
- Pirlindole
- Toloxatone
Selective MAO-B inhibitors
- Rasagiline
- Selegiline
- Safinamide
Linezolid is an antibiotic drug with weak MAO-inhibiting activity.
Methylene blue, the antidote indicated for drug-induced methemoglobinemia, among a plethora of other off-label uses, is a highly potent, reversible MAO inhibitor.
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Mechanism of action of Monoamine Oxidase Inhibitor
Although the mechanisms for MAOIs beneficial action in the treatment of Parkinson’s disease are not fully understood, the selective, irreversible inhibition of monoamine oxidase type B (MAO-B) is thought to be of primary importance. MAO-B is involved in the oxidative deamination of dopamine in the brain. MAOIs binds to MAO-B within the nigrostriatal pathways in the central nervous system, thus blocking microsomal metabolism of dopamine and enhancing the dopaminergic activity in the substantial nigra. MAOIs may also increase dopaminergic activity through mechanisms other than inhibition of MAO-B. At higher doses, MAOIs can also inhibit monoamine oxidase type A (MAO-A), allowing it to be used for the treatment of depression.
Indications of Monoamine Oxidase Inhibitors
Newer MAOIs (typically used in the treatment of Parkinson’s disease) and the reversible MAOI moclobemide provide a safer alternative and are now sometimes used as first-line therapy.
- Fainting
- Panic disorder with agoraphobia,
- Social phobia,
- Atypical depression or
- Mixed anxiety disorder and
- Depression,
- Bulimia,
- Post-traumatic stress disorder
- Borderline personality disorder.
- Bipolar depression
- Obsessive-compulsive disorder (OCD),
- Trichotillomania,
- Dysmorphophobia, and
- Avoidant personality disorder,
- Treatment of Parkinson’s disease
- Migraine prophylaxis.
- Inhibition of both MAO-A and MAO-B is used in the treatment of clinical depression and anxiety.
- Dysthymia complicated by panic disorder or hysteroid dysphoria, which involves repeated episodes of depressed mood in response to feeling rejected.
Contra-Indications of Monoamine Oxidase Inhibitors
- Malignant melanoma
- Severe mental disorder with loss of personality & reality
- Abnormal movements of facial muscles and tongue
- Abnormal heart rhythm
- Blood pressure drop upon standing
- Liver problems
- Kidney disease with the reduction in kidney function
- Allergies to monoamine oxidase inhibitors
Side Effects of Monoamine Oxidase Inhibitors
The most common
- Dizziness
- Orthostatic hypotension
- Xerostomia (dry mouth)
- A headache
- Fatigue
- Skin reactions
- Hypotension
- Anxiety
- Constipation
- Sedation (dose-dependent)
- Nausea/vomiting
- Weight gain/loss
- Pain below the ear (from salivary gland)
- Erectile dysfunction
More common
- Abdominal or stomach pain, discomfort, or tenderness
- chills or fever
- difficulty with moving
- headache, severe and throbbing
- joint or back pain
- muscle aching or cramping
- muscle pains or stiffness
- chest pressure or squeezing pain in the chest
- discomfort in arms, shoulders, neck or upper back
- excessive sweating
- feeling of heaviness, pain, warmth and/or swelling in a leg or in the pelvis
- sudden tingling or coldness in an arm or leg
- sudden slow or difficult speech
- sudden drowsiness or need to sleep
- fast breathing
- sharp pain when taking a deep breath
- fast or slow heartbeat
- coughing up blood
- rust colored urine
- decreased amount of urine
Rare
- Anxiety
- change in vision
- chest pain or tightness
- confusion
- cough
- Agitation
- arm, back, or jaw pain
- blurred vision
- chest pain or discomfort
- convulsions
- extra heartbeats
- fainting
- hallucinations
- a headache
- irritability
- lightheadedness
- mood or mental changes
- muscle pain or cramps
- muscle spasm or jerking of all extremities
- nervousness
Drug Interactions of Monoamine Oxidase Inhibitor
MAO inhibitors may interact with the following drug, supplements, & may change the efficacy of drugs
- benzodiazepines (e.g., alprazolam, diazepam, lorazepam)
- atomoxetine
- cyclobenzaprine
- dextroamphetamine
- levodopa
- beta-agonists (e.g., formoterol, salbutamol, salmeterol)
- other beta-blockers (e.g., propranolol, metoprolol)
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- cyclosporine
- dexamethasone
- diuretics (water pills; e.g., furosemide, hydrochlorothiazide)
- duloxetine
- lapatinib
- levodopa
- sympathomimetic medications (e.g., pseudoephedrine, phenylephrine, ephedrine)
- tramadol
- lidocaine
- MAO inhibitors (e.g., phenelzine, moclobemide, )
- macrolide antibiotics (e.g., azithromycin, clarithromycin, erythromycin)
- nilotinib
- nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, naproxen)
- pentoxifylline
- phosphodiesterase-5-inhibitors (e.g., sildenafil, tadalafil)
- selective serotonin reuptake inhibitors (SSRI; e.g., fluoxetine, paroxetine, sertraline)
- tricyclic antidepressants (e.g., amitriptyline, doxepin, nortriptyline)
MAOIs that have been withdrawn from the market
- Nonselective MAO-A/MAO-B inhibitors
- Hydrazines
- Benmoxin
- Iproclozide
- Iproniazid
- Mebanazine
- Octamoxin
- Pheniprazine
- Phenoxypropazine
- Pivalylbenzhydrazine
- Safrazine
- Non-hydrazines
- Caroxazone
- Hydrazines
- Selective MAO-A inhibitors
- Minaprine
List of RIMAs
Marketed pharmaceuticals
- Brofaromine
- Caroxazone
- Eprobemide
- Methylene blue
- Metralindole
- Minaprine
- Moclobemide
- Pirlindole
- Toloxatone
References
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