CNS-DEPRESSION-PART-IV-Contd..

DEPRESSION-TREATMENTS-Contd...

Mono Amine Oxidase Inhibitors (MAOIs):-

Mono Amine Oxidase is a typical enzyme available widely in our body especially in the neuronal mitochondria(a small tissue composed of endothelial cells present within the nerve synapses)in the CNS, liver, and the entire digestive tract. A major portion is present in the liver. Its main duty is to decompose any monoamines(a chemical which contains only one amino -NH2- group in its molecular structure) such as all excess catecholamines neurotransmitters like norepinephrine, epinephrine, dopamine etc.etc. by oxidation. This enzyme is protecting our CNS from overstimulation by the excess monoamine neurotransmitters.

These MAOs are grouped into two as MAO-A; and MAO-B

The former is present mostly in the mitochondrial cells of CNS presynaptic nerves, liver, lungs, placenta, and GI tract. This group is responsible to deaminate(decompose) norepinephrine, epinephrine, serotonin, and melatonin.

The latter group is mainly present in the blood platelets and is responsible to decompose phenylethylamine and benzylamine.

Dopamine and tyramine are affected by both the groups with a little more effect by MAO-B

Mechanisms MAOIs:-

Within the neuronal presynapses, these inhibitors act on MAO-A and block its decomposing effect of the neurotransmitters such as norepinephrine, and serotonin and thereby cause accumulation of the transmitters sufficiently to release from the storage into the synaptic space to act on their respective receptors present at the post synapse. Similarly, blockade of MAO-B will result in the accumulation and release of Dopamine into the synapse to act on its receptor.

All MAOIs are mostly nonspecific except selegiline which specific to block MAO-B and are widely used in Parkinson's Disease in which there is insufficient dopamine present at the synapse and hence it is of little importance here.

Clinical Indications of nonspecific MAOIs:-

Atypical depression, like phobias.

Kinetics:

1. Orally well absorbed

2. Metabolized in the liver by acetylation.

MAOIs are generally having half-life 2 to 3 hours. But they require 3 to 4 weeks of treatment to attain the steady-state plasma concentration.

Side Effects:-

1.Hypertensive crisis such as headache, arrhythmias, and stroke. Hence the patient should be advised not to take tyramine rich foods like seasoned cheese, chicken liver, chocolates, beer, and red wine.

The hypertensive crisis will also occur if taken MAOIs along with any opioids such as meperidine.
2.Orthostatic hypotension
3.Anticholinergic effects such as dry mouth, blurred vision, and weight gain.