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Pharmacology d-Deprenyl: Vyvanse for dmeth and neuroprotection bonus

This thread contains discussion about a Pharmacology-related topic
MephedroneCandy

MephedroneCandy

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I ordered 10 grams of S(+)-Deprenyl to treat my ADHD. It is the opposite enantiomer of the MAO-B inhibitor Selegiline.
It is a prodrug for dextromethamphetamine mainly and dextroamphetamine. The metabolism is also very efficient as you get about 75% back in amphetamines.
Through oral ROA in a few hours half gets produced, through others the half life is 20 hours, so dextrometahamphetamine production is extremely stable over the whole 24 hours of the day.
About this substance there are a lot of threads on internet forums from people interested in it, but I didn't saw any experience. I hope to write mine.

Consider everything as dextro enantiomers as the metabolism is stereoselective:

MY OWN RATIONALE:
People with ADHD sleep better on stimulants than without. When sleep is difficult after taking it, it is because they are withdrawal.
ADHD rebound is the most problematic side effect of stimulants and the cause of insomnia. Living everyday through peaks and withdrawals lower the quality of life.
What is normally called comedown in reality is the withdrawal and is the cause of xerostomia, bruxism, stiffness and other side effects.
Vyvanse and other prodrugs had been developed to address this, but they are not available in most countries or they cost a lot.
S(+)-Deprenyl is legal in most countries, altough it is not a research chemical as the drug has been researched a lot for decades.
Also, dextromethamphetamine has higher therapeutic value for a lot of patients than dextroamphetamine, especially considering the side effects.
Dextromethamphetamine is reported to have less cardiovascular side effects than amphetamine even though it has the same DAT/NAT affinity ratio.
This is because dopamine release it is indirecrly potentiated by its sigma1 antagonism propriety since it facilitates DAT reversal.
S(+)-Deprenyl has a very high affinity for sigma1, thus it exalts this favorable mechanism of action and potentiates dopamine release even more.
Selegiline has been shown to be neuroprotective by preventing the damage of short and long term methamphetamine neurotoxicity.
Hopefully, S(+)-Deprenyl still has the ability to inhibit most mao-b enzymes as it would be neuroprotective and increases PEA.
PEA's NDRI properties might counteract amphetamines induced reuptake transporters downregulation.
In the end, it might be a very good prodrug to get EXTREMELY stable h24 stimulation without neurotoxicity nor tolerance!

Any thoughts before it arrives?

en.wikipedia.org

D-Deprenyl - Wikipedia

en.wikipedia.org en.wikipedia.org
 
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This sounds rather dangerous. Your dose response curve is going to be fairly steep with combining a monoamine releaser with a MAO-B inhibiting prodrug. Think a catecholaminergic PMA at worst.

Deprenyl and phenethylamine has put a handful of rather smart bluelighters in the hospital for hypertensive crises.

If you must do this, titrate your dose in very small increments, and watch out for buildup of methamphetamine in your system if taken often. Preferably inform somebody what you are doing so that medical attention will be swift.
 
Skorpio said:
This sounds rather dangerous. Your dose response curve is going to be fairly steep with combining a monoamine releaser with a MAO-B inhibiting prodrug. Think a catecholaminergic PMA at worst.

Deprenyl and phenethylamine has put a handful of rather smart bluelighters in the hospital for hypertensive crises.

If you must do this, titrate your dose in very small increments, and watch out for buildup of methamphetamine in your system if taken often. Preferably inform somebody what you are doing so that medical attention will be swift.
Click to expand...
I combined selegiline with stimulants a ton of times, including meth. It is not dangerous, as explained in the study I linked it is neuroprotective too. In reality new HQ research shows that mao-b is not responsible for dopamine degradation although it has affinity for it, instead MAO-A degrades dopamine too.
Plus, as I said the S isomer has a lot less mao-b affinity, but hopefully it is enough to still inhibit mao-b at normal dosages when used as prodrug.
Phenetylamine has not the same pharmacological profile of common stimulants.

www.nature.com

Redefining differential roles of MAO-A in dopamine degradation and MAO-B in tonic GABA synthesis - Experimental & Molecular Medicine

The inhibition of two forms of an enzyme that modulate key processes in the brain has different benefits for patients with Parkinson’s disease than previously thought. Monoamine oxidase (MAO) is present in the brain as MAO-A and MAO-B, both of which were thought to be involved in dopamine...
www.nature.com www.nature.com
 
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That's interesting about the dopamine metabolism being MAO-A dependant in the striatum.

Do you know if high doses of D-deprenyl will block MAO-A as L-deprenyl does?
 
What doses have you been taking? The sigma affinity I was not aware of, and interests me.

-GC
 
Skorpio said:
That's interesting about the dopamine metabolism being MAO-A dependant in the striatum.

Do you know if high doses of D-deprenyl will block MAO-A as L-deprenyl does?
Click to expand...
d-deprenyl does not have MAO-A affinity at all.
G_Chem said:
What doses have you been taking? The sigma affinity I was not aware of, and interests me.

-GC
Click to expand...
10 mg of selegiline oral to selectively inhibit mao-b and to have neuroprotection.
 
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I have exciting new research on d-deprenyl!
I predicted that with 30 mg of d-deprenyl oral one can reach a peak of 10 mg of dmeth that lasts for 6 hours (ONLY the peak!).
This prediction is pessimistic because probably what is perceived as peak is a bigger portion of the graph and also I don't consider dextroamphetamine metabolites. In reality the peak might be of 10 hours at least orally.

I had no idea of the dosage to take and the duration, so I put the function for calculating the concentration of a metabolite of a substance in plasma into a graphing calculator!
I made a desmos page that plots the resultant dosage of the active drug in plasma over time. It has instructions too.
Just put the half-life of the prodrug (d-deprenyl), the active metabolite (dextromethamphetamine), and the reference d-deprenyl dosage. Assume a conversion rate of 60%, so reduce the concentration shown in the graph by 40%.
www.desmos.com

Drug metabolite plasma concentration curve

www.desmos.com www.desmos.com
Here is a screenshot of two example graphs, 10 mg oral and transdermal/any other ROA respectively.

From these two you can get an idea of the duration of the peak and the concentration of plasma dmeth in relation to the dosage taken.
 
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I made the calculations for chronic dosing using any other ROA than oral such as intramuscular which is the one I want to try for the first report.
By taking a single dose of 90 mg every 24 hours the higher dextromethamphetamine plasma concentration you get is 34 mg and the lowest is 29 mg (at the end of the 24 hours).
It is SO stable, it is like having a portable meth infusor and living always in the peak lol.

It is the dosage I will try for my first report.
This is another desmos page I made to calcolate the active drug concentration in chronic dosing:
www.desmos.com

Chronic active drug plasma concentration curve

www.desmos.com www.desmos.com
 
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IS Depranyl a prodrug of dexamphetamine? I thought the entire point of the N-ethynyl was that the body cannot remove it - that's WHY it's an MAOI.

I would expect the (S) isomer to be a MORE potent MAOI.
 
AlsoTapered said:
IS Depranyl a prodrug of dexamphetamine? I thought the entire point of the N-ethynyl was that the body cannot remove it - that's WHY it's an MAOI.

I would expect the (S) isomer to be a MORE potent MAOI.
Click to expand...
Have you read at least the wikipedia page? And it is a prodrug of dexmeth
 
MephedroneCandy said:
Have you read at least the wikipedia page? And it is a prodrug of dexmeth
Click to expand...

No - I only read reference, not public pages put together with random strangers with no formal qualifications working under fke names. To be accepted as reference, a process that involves peer review and defence of the findings given.

IF you read the rat discrimination reference on that Wiki page, stimulant activity was only noted at VERY high doses 17.0 - 30mg/Kg.

Now I'm the first to say 'well, that's in rats' but they also noted that both isomers were equally active as MAOIs making them rather an unwise choice as a psychostimulant.
 
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