Mechanism of action therapeutic uses and side effects of Iproniazid
Which pills do you take when you are sad and need to elevate your mood? Mostly, these are antidepressants. One of them is iproniazid.
This chemical element was introduced in the medical industry in 1958. It is the first drug of the monamine-oxidase inhibitor series. It was used widely as antidepressants until the iproniazid side effects came out to be liver damage.
Before it was introduced, it was considered similar to the function of the antituberculosis drug isoniazid. This is similar in structure to iproniazid. But, what is the iproniazid structure? And how does it look like?
Iproniazid Structure
The structure of iproniazid is:
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Its chemical formula is: C9H13N30
The iproniazid structure is chemically, in both structure and reactivity, similar to isoniazid. It is a small molecule that was developed as the first antidepressant. This molecule prevents the breakdown of norepinephrine. It is a brain neurotransmitter. This substance is concerned with emotional stimulation. This process happens mainly through the inhibition of enzyme monoamine oxidase.
The molecular weight of iproniazid is 179.22.
Its melting point is between 161-161.5
It is a carbohydrazide and a member of pyridines.
Its name according to the IUPAC nomenclature is N'-propan-2-yl-pyridine-4-carbohydrazide.
Iproniazid acts by increasing the size and concentration of granular vesicles. Moreover, it has a protective effect.
Monoamine Oxidase Inhibitors
To treat the patients for tuberculosis pharmacologically, isoniazid and its derivatives were introduced in 1951. Iproniazid worked by inhibiting the enzyme MAO, becoming an iproniazid antidepressant and it worked by uplifting the mood of the patients.
After gaining a deeper understanding of this drug, it was found out that this drug also benefitted in treating chronic pain. One of the most notable among them was an intractable headache. However, with this came the realization of its limit of clinical utility.
But, with the introduction of TCAs, the MAOIs took a backfoot. The MAOIs are a heterogeneous group of drugs. They work by blocking the oxidative deamination of biogenic amines. This process leads to a release of larger-than-normal amounts of these amines.
The MAOIs can be easily absorbed in the mouth, and their metabolization in the liver primarily takes place through acetylation.
The most commonly used MAOIs are isocarboxazid, phenelzine and tranylcypromine. These are the non-selective inhibitors of MAO. Among them, phenelzine is the one that is used most commonly for the treatment of pain. Initially, the dose intake of phenelzine should be 15mg. But, with time, it can be increased by 15mg every week. The efficacy can dictate a total of 60mg.
Even after this dose, if the patient does not get relief, they can additionally intake amitriptyline in a dose of 10mg. Do not abruptly discontinue the intake of phenelzine.
FAQs on Iproniazid as a Monoamine Oxidase Inhibitor Drug
1. What is Iproniazid?
Iproniazid is a monoamine oxidase inhibitor (MAOI) originally developed as an anti-tuberculosis drug that was later found to have antidepressant effects.
- It is a derivative of isoniazid.
- It inhibits the enzyme monoamine oxidase (MAO).
- It was one of the first drugs used to treat major depressive disorder.
2. How does Iproniazid work in the brain?
Iproniazid works by inhibiting monoamine oxidase (MAO), increasing levels of mood-regulating neurotransmitters in the brain.
- MAO normally breaks down serotonin, norepinephrine, and dopamine.
- Inhibition of MAO leads to higher concentrations of these neurotransmitters.
- Elevated monoamines improve mood and reduce depressive symptoms.
3. What type of drug is Iproniazid?
Iproniazid is an irreversible, non-selective monoamine oxidase inhibitor (MAOI).
- It inhibits both MAO-A and MAO-B enzymes.
- The inhibition is irreversible, meaning new enzymes must be synthesized to restore activity.
- It affects neurotransmitter metabolism throughout the nervous system.
4. Why was Iproniazid used as an antidepressant?
Iproniazid was used as an antidepressant because it elevated brain monoamines and improved depressive symptoms.
- Patients treated for tuberculosis showed unexpected mood elevation.
- This led to its use in treating clinical depression.
- It helped establish the monoamine hypothesis of depression.
5. Why was Iproniazid discontinued?
Iproniazid was discontinued mainly due to severe liver toxicity and safety concerns.
- It was associated with hepatotoxicity (liver damage).
- It caused dangerous interactions with tyramine-containing foods.
- Safer antidepressants were later developed.
6. What are the side effects of Iproniazid?
The major side effects of Iproniazid include liver toxicity, hypertension, and neurological symptoms.
- Hepatitis and liver failure in severe cases.
- Hypertensive crisis when combined with tyramine-rich foods.
- Dizziness, insomnia, and agitation.
7. What is the mechanism of action of Iproniazid?
The mechanism of action of Iproniazid involves irreversible inhibition of monoamine oxidase enzymes.
- It binds covalently to MAO-A and MAO-B.
- This prevents oxidative deamination of monoamines.
- Neurotransmitter levels increase in synaptic clefts.
8. What is the relationship between Iproniazid and monoamine oxidase?
Iproniazid inhibits monoamine oxidase, the enzyme responsible for breaking down key neurotransmitters.
- Monoamine oxidase (MAO) regulates serotonin, dopamine, and norepinephrine levels.
- Iproniazid blocks MAO activity.
- This results in enhanced neurotransmission and mood elevation.
9. How did Iproniazid contribute to the monoamine hypothesis of depression?
Iproniazid supported the monoamine hypothesis by showing that increasing monoamine levels improves depression.
- Depressed patients improved when MAO was inhibited.
- This suggested low monoamine neurotransmitters may cause depression.
- It guided the development of modern antidepressants.
10. Is Iproniazid still used in modern medicine?
Iproniazid is not commonly used today due to safety concerns and the availability of safer alternatives.
- High risk of liver toxicity.
- Risk of hypertensive crisis with dietary tyramine.
- Replaced by safer antidepressants such as SSRIs and newer MAO inhibitors.
