What is the Difference Between MAO-A and MAO-B Inhibitors

The main difference between MAO-A and MAO-B inhibitors is their type of inhibition. MAO-A inhibitors inhibit the activity of the MAO-A enzyme, while MAO-B inhibitors inhibit the action of the MAO-B enzyme. Clorgyline is an example of a selective MAO-A inhibitor, while selegiline is an example of a selective MAO-B inhibitor.

MAO-A and MAO-B inhibitors are two types of inhibitors of the isoenzymes encoded in the human X chromosome. They are effective antidepressants for treatment-dependent depression and atypical depression.

Key Areas Covered

1. What are MAO-A Inhibitors
– Definition, Features, Importance
2. What are MAO-B Inhibitors
– Definition, Features, Importance
3. Similarities Between MAO-A and MAO-B Inhibitors
– Outline of Common Features
4. Difference Between MAO-A and MAO-B Inhibitors
– Comparison of Key Differences

Key Terms

MAO-A Inhibitors, MAO-B Inhibitors, Monoamine Oxidase A, Monoamine Oxidase B

What are MAO-A Inhibitors

MAO-A (Monoamine Oxidase A) inhibitors are a class of drugs that inhibits the action of isoenzyme MAO-A. Clorgyline and Moclobemide are examples of selective irreversible and reversible inhibitors, respectively. Clorgyline is structurally related to pargyline, which is an antidepressant. But, it is never marketed. On the other hand, Moclobemide is a RIMA (reversible inhibitor for MAO-A), and it is used to treat depression and social anxiety. The brand names of Moclobemide include Amira, Aurorix, Clobemix, Depnil, and Manerix. Importantly, it does not increase blood pressure levels compared to older irreversible and non-selective MAO-A inhibitors that cause severe blood pressure rises with combinations.

Figure 1: Clorgiline

Furthermore, Moclobemide has a relatively fast-onset action compared to other antidepressant drugs. It is important for treating unipolar depression, psychotic depression, agitated depression, bipolar depression, dysthymia, social phobia, smoking cessation, panic disorders, ADHD, fibromyalgia, and migraine. Further, the substrates of the MOA-A include 5-HT, noradrenaline, and dopamine.

What are MAO-B Inhibitors

MAO-B (Monoamine Oxidase B) inhibitors are a class of drugs that inhibits the action of isoenzyme MAO-B. Selegiline and lazabemide are examples of selective irreversible and reversible inhibitors, respectively. Selegiline is a drug used to treat Parkinson’s disease and major depressive disorder. As an MAO-B inhibitor, selegiline is a selective and irreversible inhibitor, increasing dopamine levels in the brain. Large doses also inhibit MAO-A, increasing serotonin and norepinephrine levels in the brain.

Figure 2: Selegiline

Moreover, selegiline is important to treat the symptoms of Parkinson’s disease. It is often used as an adjunct drug, such as levodopa. In contrast, lazabemide is a selective, reversible MAO-B that was developed but not marketed as an antiparkinsonian. Beta-phenylethylamine and benzylamine are the substrates for the MAO-B.

Similarities Between MAO-A and MAO-B Inhibitors

• MAO-A and MAO-B are two types of MAO-A and MAO-B inhibitors, respectively.
• They are effective antidepressants for treatment-dependent depression and atypical depression.
• They are important in treating panic disorder, social anxiety disorder, Parkinson’s disease, and several other disorders.
• Phenelzine and tranylcypromine are nonselective MAO inhibitors.
• Mixed substrates for the MAO-A and MAO-B are dopamine and tyramine.

Difference Between MAO-A and MAO-B Inhibitors

Definition

MAO-A inhibitors refer to a class of drugs that inhibits the activity of the MAO-A enzyme, while MAO-B inhibitors refer to a class of drugs that inhibit the action of the MAO-B enzyme.

Irreversible Selective Inhibitors

Clorgyline is an example of an irreversible selective MAO-A inhibitor, while selegiline is an example of an irreversible selective MAO-B inhibitor.

Reversible Selective Inhibitors

Moclobemide is an example of a reversible, selective MAO-A inhibitor, while lazabemide is an example of a reversible, selective MAO-B inhibitor.

Selective Substrates

5-HT, noradrenaline, and adrenaline are the selective substrates for the MAO-A inhibitors, while beta-phenylethylamine and benzylamine are the selective substrates for MAO-B inhibitors.  

Cellular Localization

MAO-A cellular localization is in synaptic neurons, CNS, placenta, GI tract, hepatocytes, and many cell types. Meanwhile, MAO-B cellular localization is in astrocytes, platelets, peripheral cell types, and serotonergic neuronal cell bodies in raphe nuclei.

Conclusion

In brief, MAO-A and MAO-B inhibitors are two classes of drugs that are antidepressants given for treatment-dependent depression and atypical depression. MAO-A inhibitors are a class of drugs that inhibits the enzyme MAO-A. Clorgyline and Moclobemide are examples of selective MAO-A inhibitors. Also, the selective substrates for MAO-A inhibitors include 5-HT, Noradrenaline, and adrenaline. Moreover, cellular localization of the MAO-A inhibitors is in synaptic neurons, CNS, placenta, GI tract, and hepatocytes.

In comparison, MAO-B is another class of drugs that inhibits the MAO-B enzyme. Selegiline and lazabemide are examples of selective MAO-B inhibitors. Selective substrates for the MAO-B inhibitors are beta-phenylethylamine and benzylamine. Besides, cellular localization for MAO-B inhibitors is in astrocytes, platelets, peripheral cell types, and serotonergic neuronal cell bodies in raphe nuclei. Therefore, the main difference between MAO-A and MAO-B inhibitors is their type of inhibition.

References:

1. Finberg JP, Rabey JM. Inhibitors of MAO-A and MAO-B in Psychiatry and Neurology. Front Pharmacol. 2016 Oct 18;7:340. doi: 10.3389/fphar.2016.00340. PMID: 27803666; PMCID: PMC5067815

Image Courtesy:

1. “Clorgiline” By Fvasconcellos – Own work (Public Domain) via Commons Wikimedia
2. “Selegiline” By Harbin – Own Work (Public Domain) via Commons Wikimedia