Clorgyline

• In summary, the most potent irreversible MAO-A inhibitors in order is: Clorgyline > Nardil (Phenelzine) > Parnate (Tranylcypromine) > Marplan (Isocarboxazid)
• Comparing the MAO-A inhibition potency; Clorgyline (IC50 = 4.2 nM) > Nardil (IC50 = 15 nM) > Parnate (IC50 = 237 nM) > Marplan (IC50 = 4 800 nM) [x, x]
• Selegiline (IC50 = 970 nM), Pargyline (IC50 = >2 000 nM), and Rasagiline are selective for MAO-B and are weak MAO-A inhibitors [x]
• Clorgyline is the only non MAO-B inhibitor out of the irreversible MAOIs, so Clorgyline lacks downsides associated with unselective MAO-A/B inhibition such as excessive monoamine buildup, leading to undesirable effects, seen with Parnate [x]
• Clorgyline lasts all day because it irreversibly inhibits MAO-A, meaning that the MAO-A enzymes are permanently inhibited and must be restored with newly created MAO-A enzymes. The irreversible MAOI, Parnate, takes 48 hours to restore ~50%. Whereas the reversible MAOI, Moclobemide, has a 1 – 2 hr half-life and completely reverses within 24 hr [x, x]

Discussing Clorgyline targets other than MAO-A/B

• Clorgyline is possibly a very high affinity sigma-1 agonist (Ki = 3.2 nM), since its CA3 NMDA potentiation is prevented by the sigma-1 antagonists, Haloperidol and BMY-14802. But Clorgyline becomes a sigma-1 antagonist at higher intravenous mcg/kg doses in rats similarly to Sertraline, which is difficult to accurately convert to a human equivalent dose because they weren’t orally administered in the study [x, x]
• Clorgyline binds to Imidazoline I2 with extremely high affinity (Ki = 0.04 nM = 40 pM), as it’s in the pM range, but with an unknown action. This receptor currently has low research on it [x, x]