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Clorgyline (hydrochloride) is an irreversible, potent and selective monoamine oxidase (MAO) A inhibitor with Ki values of 0.054 and 58 μM and IC50 values of 0.0012 and 1.9 μM for MAO-A and MAO-B, respectively [1][2].

Monoamine oxidases (MAOs) are FAD depending enzymes and exists in two forms, namely MAO-A and MAO-B. MAOs are responsible for the regulation and metabolism of major monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT), norepinephrine (NE), and dopamine (DA). MAO-A preferentially oxidizes serotonin. Human MAO-A inhibitors are antidepressants and antianxiety agents [1].

Clorgyline is an irreversible, potent and selective MAO-A inhibitor. In wild-type mice, clorgyline significantly inhibited MAO-A enzymatic activity by approximately 80%. Clorgyline also significantly elevated striatal levels of 5-HT and NE, and significantly decreased DOPAC levels, suggesting that inhibition of MAO-A activity decreased the metabolism of DA. In YAC128 HD mice, clorgyline (1.5 mg/kg for 21 days) inhibited MAO-A enzymatic activity in cortical tissue by approximately 90% and significantly elevated striatal 5-HT and NE levels. Clorgyline treatment also improved anxiety-like phenotypes and reduced depressive-like behavior [3].

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