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What was the first MAOI
- Iproniazid, an anti-TB agent
- Hepatotoxic
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What are the MAOIs?
- Nonselective: hydrazine derivatives (e.g., isocarboxazid, phenylhydrazine) and nonhydrazine derivatives (e.g., tranylcypromine)
- Selective Reversible MAOAI: Moclobemide
- MAOBI: Selegiline
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What are the subtypes and functions of MAO?
- MAO-A and MAO-B
- Both present in brain and other organs
- MAO-A mostly in D and NE neurons
- MAO-B mostly in 5-HT neurons
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What are the main substrates for MAOA and MAOB
- The main substrates for MAO-A are epinephrine, NE, and 5-HT.
- The main substrates for MAO-B are phenylethylamine, phenylethanolamine, tyramine, and benzylamine.
- DA and tryptamine are metabolized by both isoenzymes.
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What are the inherited disorders associated with MAOI?
- A rare inherited disorder, Norrie’s disease, is characterized by deletion of both genes; patients with this disorder have very severe mental retardation and blindness.
- Another rare inherited disorder is Brunner syndrome, caused by a mutation in the MAO-A gene. It is characterized by impulsive aggressiveness and mild mental retardation
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What is the cofactor for MAO and where is the enzyme usually found?
- The enzyme is primarily found in the outer mitochondrial membrane;
- flavin adenine dinucleotide is a cofactor for both MAO-A and MAO-B.
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Although DA is considered to be a mixed substrate for both MAO-A and MAO-B, the breakdown of DA in the striatal regions of the brain is preferentially by ....
MAO-B
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What is the relationship of MAOA levels in the brain and major depression?
MDD is associated with higher MAOA in the brain
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What is the mechanism of action of MAO?
- MAO is bound to the outer surface of the plasma membrane of the mitochondria
- MAO is unable to deaminate amines that are present inside stored vesicles and can metabolize only amines that are present in the cytoplasm.
- As a result, MAO maintains a low cytoplasmic concentration of amines within the cells. Inhibition of neuronal MAO produces an increase in the amine content in the cytoplasm.
- Initially, it was believed that the therapeutic action of MAOIs was a result of this amine accumulation, but secondary adaptive mechanisms might also have a role.
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What is the effect of MAOIs after several week of treatment?
Reduction in the number of beta, alpha, 5HT2 and 5HT3 receptors
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What are the MAOIs?
- hydrazine derivatives: phenelzine and isocarboxazid)
- nonhydrazine derivative: tranylcypromine
- irreversible MAOB inhibitor: Selegiline
- Reversible MAOA inhibitor: Moclobemide
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What are other mechanisms of MAOIs?
- Inhibition of MAO uptake
- - tranylcypromine is similar to amphetamines and activating
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What are the indications for MAOIs?
- Atypical depression
- dysthymia
- Panic disorder (irreversible better; at first might worsen)
- Social anxiety disorder (irreversible better)
- Maybe GAD and PTSD (less evidence)
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What is the significance of acetylation in patients on Phenelzine?
slow acetylators improve more with phenelzine than do fast acetylators
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What is the comparable efficacy of MAOIs and SSRIs or TCAs in treating atypical depression?
MAOIs are superior to TCAs, but not SSRIs, in treating atypical depression
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What are the most common Side effects of MAOIs?
- Dizziness, headache, dry mouth, insomnia, constipation, blurred vision, nausea, peripheral edema, forgetfulness, fainting spells, trauma, urinary hesitancy, weakness, and myoclonic jerks.
- Loss of weight and appetite may occur with isocarboxazid use
- Elevated liver enzymes
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When is necessary to do LFTs in patients who are on MAOIs?
Liver function tests must be done when patients have symptoms such as malaise, jaundice, and excessive fatigue.
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