Microdosing Selegiline / deprenyl 0.8mg strong effect. Questions about how the MAO enzymes actually work?

[yaesutom]

I have had a bunch of 5mg deprenyl pills from India for months but was afraid or just not sure when I felt like it would be a good time to experiment. I currently take Desoxyn (most days).

I dropped one 5mg tablet into a 5ml vial and filled it with 5ml water. Let it dissolve fully / shook up etc. Then I took less than 1mg.. probably 0.75-0.8mg worth, did not even hold it in my mouth long (since sublingual can be much more bioavailable).

Well like wow - COULD be placebo but damn that stuff seems kinda strong for such a small dose? It amplified the desoxyn quite a lot. Maybe felt 2x... more or less..

------
What I am curious about is how these MAO systems work. I am trying to imagine in my head, like what does 0.8mg do, does it "kill" / destroy like 5% of the enzymes on day 1? what if you take 1mg every day for a week, does it kill 5% daily, or is this going to be on a curve - like 5% day one, 4% day 2, 3.5% day 3, 3.2% day 4... Or if you take a low enough of a dose, is your body able to replace the killed off MAO enzymes fast enough so that you can reach a steady state of some number % that just kinda stays at that level?

I will see what kind of research AI can dig up about it but just super curious because 1mg kind of kicked my ass with the desoxyn but i feel really great the next day (did not take any more deprenyl). I will prob try even less tomorrow, like 0.5mg and just be careful with the desoxyn dosage.

 

[Deleted member 576750]

it doesn't destroy the enzymes but irreversibly deactivates them. I don't think anyone could tell you how much MAO-B it would deactivate at a specific dose but it does take time for your cells to create more of the enzyme to replace what was deactivated. I think the general rule used by clinicians is that they need to know about MAOI use within the past two weeks when you go in for surgery or other procedures, but I could be wrong on that number as I'm going by memory

 

[Skorpio]

it doesn't destroy the enzymes but irreversibly deactivates them. I don't think anyone could tell you how much MAO-B it would deactivate at a specific dose but it does take time for your cells to create more of the enzyme to replace what was deactivated. I think the general rule used by clinicians is that they need to know about MAOI use within the past two weeks when you go in for surgery or other procedures, but I could be wrong on that number as I'm going by memory

^good info

Building off of that, you do eventually reach a steady state with deprenyl where MAO-B is pretty much all inhibited. At higher doses MAO-A gets inhibited too.

I would recommend extreme caution with this combo. Until you get to steady state (which is going to be hard to calculate for you without knowing a lot of ground truths regarding your physiology), combining with desoxyn will be like shooting a moving target.

Waiting a week or two of steady deprenyl dosing should at least cause things to stabilize.

That being said, deprenyl and stimulants has historically sent a lot of bluelighters to the ER with hypertensive crises. Be extremely careful with this combo, as chasing a buzz can become dangerous quick. In my head this combo is similar to combining opioids and benzos. People do it frequently without any problems, but conversely it is a combo over-represented in adverse outcomes.

 

[yaesutom]

^good info

Building off of that, you do eventually reach a steady state with deprenyl where MAO-B is pretty much all inhibited. At higher doses MAO-A gets inhibited too.

I would recommend extreme caution with this combo. Until you get to steady state (which is going to be hard to calculate for you without knowing a lot of ground truths regarding your physiology), combining with desoxyn will be like shooting a moving target.

Waiting a week or two of steady deprenyl dosing should at least cause things to stabilize.

That being said, deprenyl and stimulants has historically sent a lot of bluelighters to the ER with hypertensive crises. Be extremely careful with this combo, as chasing a buzz can become dangerous quick. In my head this combo is similar to combining opioids and benzos. People do it frequently without any problems, but conversely it is a combo over-represented in adverse outcomes.

Well honestly I could not really find much (any?) any posts or experiences by anyone who actually got a hypertensive crisis from the combo, or other stims. I do find a ton of people saying they do combine them without issues, and eat all types of food etc. Its not my first time experimenting with MAOIs, I am interested in neuroprotective qualities and just to see if it will boost the stimulant. It did seem to just for that one day - last two days I have taken around 0.5mg - 1.0mg each day and not sure I even notice anything this time. Could have been just placebo expectation before.. But since sublingual dose can be 1.25mg, maybe I will try 0.5mg but hold it in my mouth for 10-15 minutes.

I wonder if sublingual also bypasses the first pass metabolism like a patch would.....

I will be careful - years ago I tried taking 5mg oral daily with my daily 60mg dexedrine.. but it was a bit too much. I remember getting anxiety so I quit.

 

[red22]

Building off of that, you do eventually reach a steady state with deprenyl where MAO-B is pretty much all inhibited.

"eventually"?


"After the administration of a therapeutic dose (5–10 mg), the peak plasma concentration is reached within 30–120 min; 90% is bound to plasma proteins [60,62,63]. Within 30–90 min, platelet MAO-B activity is inhibited by 90% in PD patients, indicative of rapid cellular uptake; recovery of activity requires as long as 40 days [14,64]."

14. Fowler JS, Volkow ND, Logan J, Wang GJ, MacGregor RR, Schyler D, Wolf AP, Pappas N, Alexoff D, Shea C. Slow recovery of human brain MAO-B after l-deprenyl (selegiline) withdrawal. Synapse 1994;18:86–93.

64. Riederer P, Youdim MBH, Rausch WD, Birkmayer W, Jellinger K, Seemann D. On the mode of action of l-deprenyl in the human central nervous system. Journal of Neural Transmission 1978;43:217–26.

Foley P, Gerlach M, Youdim MB, Riederer P. MAO-B inhibitors: multiple roles in the therapy of neurodegenerative disorders. Parkinsonism Related Disorders, 6(1):25-47.


"The doses of 5 or 10 mg daily and 20 mg (i.e., 10 mg x 2) weekly induced a complete inhibition of platelet MAO-B activity from day 7 to day 28 (96.0-99.5%)."

Andreu, N., Damase-Michel, C., Senard, J. M., Rascol, O., & Montastruc, J. L. 1997. A dose-ranging study of selegiline in patients with Parkinson's disease: effect of platelet monoamine oxidase activity. Movement disorders : official journal of the Movement Disorder Society, 12(3), 293–296. doi: 10.1002/mds.870120305