Description
Why Cimoxatone as a reversible selective MAO-A inhibitor
- In summary, the best selective reversible MAO-A inhibitors in order is: Cimoxatone ≈ Befloxatone > CX-157 > Bifemelane > Moclobemide > Toloxatone
- Harmine and Harmaline, which are MAOIs from Ayahuasca MAOIs, weren’t considered because they’re unselective and have many off-targets
- Out of all the reversible MAO-A inhibitors, there are only three extremely potent and long-lasting candidates which are Cimoxatone, Befloxatone, and CX-157
- CX-157 requires 80 mg for sufficient MAO-A inhibition (72%) with a 6.0 hr half-life, Moclobemide needs 300 mg (71.48%) with a 1 – 2 hr half-life, Befloxatone needs 20 mg with a 11.1 hr half-life, and Cimoxatone needs 20 mg with a 12.4 hr half-life in humans [x, x, x, x]
- Cimoxatone (IC50 = 3 nM) is equipotent in MAO-A inhibition to Befloxatone (IC50 = 4 nM) [x]
- Cimoxatone (IC50 = 90 nM) is more potent as a MAO-B inhibitor than Befloxatone (IC50 = 300 nM) [x]
- Cimoxatone’s major metabolite, MD-770222, is a MAO-A inhibitor and has an extremely long 35 – 40 hr half-life in humans [x]
- Cimoxatone is predicted to be more lipophilic than Befloxatone, so having higher BBB permeability, by having a lipophilic Benzonitrile group instead of a Hydroxy group which is polar and impairs lipophilocity
20 mg Cimoxatone is equivalent to 300 mg Moclobemide
- At least 70% is considered “sufficient MAO-A inhibition” because it’s known that 300 mg Moclobemide (71.48%) effectively prevents the breakdown of Tryptamines with a short half-life, since 150 mg is insufficient and ≥450 mg doses negligibly prevents further degredation, making 70% the minimum standard to target
- Note that DHPG is a deaminated Norepinephrine metabolite created by MAO-A, so a reduction of DHPG indicates an increase of MAO-A inhibition
- This Befloxatone data shows a plateau starting at 10 – 20 mg for DHPG reduction, and higher doses of both Befloxatone and Moclobemide negligibly improve DHPG reduction, indicating MAO-A being sufficiently inhibited at these doses. This equates to about -80%Â DHPG reduction, since Befloxatone at 20 mg has -81%Â DHPG reduction and 300 mg Moclobemide has -80%
- Thus, 20 mg of Befloxatone and 300 mg of Moclobemide inhibit MAO-A similarly verified by matching their data on DHPG reduction and knowing that 300 mg of Moclobemide inhibits MAO-A by 71.48% [x, x, x]
- Therefore, since Cimoxatone and Befloxatone are nearly identical in their structure, IC50, and half-life; 20 mg of Cimoxatone sufficiently inhibits MAO-A
