MAOI A-PVP Red Discussion: MAOIs and A-PVP

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MAOIs and A-PVP​

Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs that work by inhibiting the activity of an enzyme called monoamine oxidase (MAO). MAO plays a crucial role in breaking down neurotransmitters in the brain, including serotonin, norepinephrine, and dopamine. These neurotransmitters are key regulators of mood, emotion, and arousal. By inhibiting MAO, MAOIs increase the levels of these neurotransmitters, which can help alleviate symptoms of depression and other mood disorders.

There are two types of MAO enzymes: MAO-A and MAO-B. MAO-A primarily breaks down serotonin and norepinephrine, while MAO-B primarily breaks down dopamine and phenylethylamine. MAOIs inhibit these enzymes, preventing the breakdown of the neurotransmitters. This leads to an increase in their levels and activity in the brain.

By inhibiting MAO, more serotonin, norepinephrine, and dopamine remain available in the synaptic cleft (the gap between neurons where neurotransmitter communication occurs). This increase in neurotransmitter levels can enhance mood, reduce anxiety, and improve energy levels, which are often impaired in depressive states.

Some MAOIs irreversibly bind to the MAO enzyme, permanently deactivating it until the body produces more enzyme (which can take weeks). Other MAOIs are reversible and temporarily inhibit the enzyme. Once the drug is cleared from the system, the enzyme's activity resumes.

Examples of MAOIs

• Phenelzine (Nardil): Irreversible, non-selective (inhibits both MAO-A and MAO-B). Primarily used to treat major depressive disorder (MDD), especially in cases that are resistant to other treatments.
• Tranylcypromine (Parnate): Irreversible, non-selective (inhibits both MAO-A and MAO-B). Similar to phenelzine, used in treatment-resistant depression.
• Moclobemide (Aurorix, Manerix): Reversible inhibitor of MAO-A (RIMA). Primarily used to treat depression and social anxiety disorder.

Alpha-Pyrrolidinopentiophenone (A-PVP), commonly known as "flakka" or "gravel," is a synthetic stimulant of the cathinone class. It's notorious for its potent stimulant effects, which can lead to severe and dangerous psychological and physical side effects.

A-PVP acts as a **reuptake inhibitor** of the neurotransmitters dopamine and norepinephrine. A-PVP inhibits this reuptake process, leading to an accumulation of dopamine and norepinephrine in the synaptic cleft. The increased levels of these neurotransmitters enhance stimulation of their respective receptors, leading to heightened alertness, energy, euphoria, and an increased sense of well-being.

The excess dopamine, particularly in the brain's reward pathways, is what contributes to the intense euphoria and potential for addiction seen with A-PVP use. Norepinephrine contributes to the stimulant effects, including increased heart rate, blood pressure, and alertness.


Combining MAOIs with A-PVP is extremely dangerous due to the severe and potentially life-threatening interactions between these substances.

1. Cardiovascular Strain: The combination of MAOIs and A-PVP significantly increases the risk of cardiovascular complications. Both drugs elevate heart rate and blood pressure, increasing the strain on the heart and blood vessels.
2. Hypertensive Crisis: MAOIs inhibit the breakdown of monoamines, including norepinephrine, leading to elevated levels in the body. A-PVP, being a potent stimulant, further increases norepinephrine release. The combination can cause a hypertensive crisis—an abrupt and severe increase in blood pressure, which can lead to strokes, heart attacks, or even death.
3. Hyperthermia: The combination can lead to uncontrolled hyperthermia (elevated body temperature) due to excessive norepinephrine and serotonin activity. This can be life-threatening if not promptly managed.
4. Metabolic Acidosis: The intense stimulation caused by A-PVP, combined with the metabolic effects of MAOIs, can lead to metabolic acidosis, a dangerous condition where the blood becomes too acidic.
5. Serotonin Syndrome: Both MAOIs and A-PVP can increase serotonin levels. MAOIs block the breakdown of serotonin, and A-PVP may indirectly enhance serotonin release. This can lead to serotonin syndrome, a potentially fatal condition caused by excessive serotonergic activity.
6. Psychosis and Agitation: A-PVP is known for its powerful stimulant effects, leading to extreme agitation, paranoia, and hallucinations. When combined with MAOIs, which also elevate dopamine levels, these effects can be exacerbated, leading to severe psychosis.

The combination of MAOIs and A-PVP is highly dangerous due to the synergistic effects on neurotransmitter systems, leading to severe and potentially fatal outcomes.

All things considered, we recommend avoiding this combination under any conditions.