How Does Iproniazid Function as a Monoamine Oxidase Inhibitor?
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 Explained: Definition, Structure & Biological Role
1. What type of drug is Iproniazid?
Iproniazid is classified as a monoamine oxidase inhibitor (MAOI). It was one of the first drugs in this class to be marketed as an antidepressant. It functions by preventing the breakdown of certain neurotransmitters in the brain, which helps to elevate mood.
2. What were the primary medical uses for Iproniazid?
Initially, Iproniazid was developed and studied as an anti-tuberculosis agent, similar to its precursor, isoniazid. However, its significant mood-lifting properties were discovered as a side effect, which led to its primary use as the first clinically effective antidepressant for treating major depressive disorders.
3. What is the mechanism of action for Iproniazid?
Iproniazid works by irreversibly inhibiting the enzyme monoamine oxidase (MAO). This enzyme is responsible for breaking down neurotransmitters like serotonin, norepinephrine, and dopamine in the brain. By blocking MAO, Iproniazid increases the concentration of these mood-regulating neurotransmitters in the synaptic cleft, leading to its antidepressant effects.
4. Why was Iproniazid withdrawn from most markets despite its effectiveness?
The primary reason for the withdrawal of Iproniazid was its significant risk of causing severe hepatotoxicity, or liver damage. A notable number of patients developed acute hepatocellular hepatitis, a serious form of liver injury, within a few months of starting the medication. The potential for fatal liver damage was considered too high a risk for its continued use.
5. How does Iproniazid differ from a tranquilizer?
Iproniazid and tranquilizers have opposite effects on the nervous system.
- Iproniazid is a stimulant antidepressant that elevates mood by increasing the levels of active neurotransmitters.
- A tranquilizer, on the other hand, is a depressant that reduces anxiety and tension by slowing down brain activity, often by enhancing the effects of the inhibitory neurotransmitter GABA.
6. What are the major side effects associated with taking Iproniazid?
Aside from the severe liver toxicity that led to its withdrawal, Iproniazid was associated with several other side effects, including:
- Hypertensive crises: A sudden, severe increase in blood pressure, especially when taken with certain foods rich in tyramine (like aged cheese and wine).
- Dizziness and orthostatic hypotension (a drop in blood pressure upon standing).
- Dry mouth, constipation, and blurred vision.
7. What is the chemical relationship between Iproniazid and Isoniazid?
Iproniazid is a chemical derivative of Isoniazid. Isoniazid is primarily an anti-tuberculosis drug. Iproniazid was synthesized from isoniazid by adding an isopropyl group. This seemingly small structural modification is what conferred the potent MAO-inhibiting property upon Iproniazid, transforming it from a tuberculosis drug into a powerful antidepressant.
8. Was Iproniazid the very first antidepressant drug?
Yes, Iproniazid is widely considered the first clinically effective antidepressant from the monoamine oxidase inhibitor (MAOI) class. Its mood-elevating effects were discovered serendipitously in the 1950s during trials for tuberculosis, which ushered in the modern era of psychopharmacology for treating depression.
