83 replies to this topic

[Reformed-Redan]

I'm wondering if there is any interest in a group buy for D-Deprenyl. I think the dextro enantiomer of selegiline has much more therapeutic value than the levo enantiomer. More info on D-deprenyl, here.

 

Obviously, given my history I won't have anything to do with the group buy; but, nevertheless would love to see this baby produced since it seems like an ideal candidate for treating ADD-PI. 

 

Edited by yadayada, 20 June 2014 - 04:37 AM.

[Ruinmir]

I'd be interested

[FW900]

This would be an interesting compound. It truly would be a game changer in the world of nootropics.

 

I think the feasibility of a group buy, given the precursors required, would be suspicious and hard to set up, particularly with a Chinese lab- especially being a customer out of the blue. If enough people showed their interest, a vendor would have better luck setting this up. Ceretropic, or New Star Nootropics, I think I have seen each mention that they would one day look into carrying deprenyl. They should abandon that, and go strictly for D-deprenyl given how cheaply regular L-deprenyl can be obtained at sites like all day chemist.

 

It probably would be the ideal drug for treating both sleep disorders and ADHD, given that it contains a very smooth acting CNS stimulant as a metabolite and acts as a catecholaminergic activity enhancer. I have no idea how CAEs work, but I imagine the D- isomer would produce more pronounced effects in regards to dopaminergic stimulation. At the same time, the (weak) MAO-B inhibition would prevent the breakdown of dopamine by MAO-B and that would mitigate some woes regarding neurotoxicity. Supplementing with memantine would further reduce concerns for neurotoxicity.

 

Whoever is interested in D-Deprenyl, should post in this thread, so vendors such as NSN and Ceretropic see the demand for this compound.

 

 

MAO-B inhibition not as pronounced as L-deprenyl is:

http://www.ncbi.nlm....pubmed/12872288

[8bitmore]

I echo the sentiment that it would be great to have vendors such as NSN and Ceretropic carry (D/L-)-deprenyl, can't personally quite be asked with group buy, like FW900 says the precursors alone will make this a hard buy (unless fortunately circumstances fly by, in which case: hurrah!).

[chemicalambrosia]

I've posted several times on this board and on reddit that I'm interested in D-Deprenyl and Amineptine. I think they are two fairly well researched compounds that should be available to the community. Some vendor could make some nice money off of them.

[Reformed-Redan]

I talked with Ceretropic. They said they're interested in procuring this. Hope it happens.

[Keizo]

Yes. Though I can't find information on the legality if I were to import it. Well, Lisdexamfetamine was not classified as narcotics until recently... Assuming in this case isomers are not automatically suspect it would not be seen as medication even. (Though I assume they may reserve the right to destroy anything they want.)

Edited by Keizo, 21 June 2014 - 06:59 PM.

[FW900]

Here are some articles I found on D-Deprenyl.

 

 

http://www.ncbi.nlm.nih.gov/pubmed/12872288 

 

D-deprenyl protects nigrostriatal neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity.

 

Selegiline (L-deprenyl) is believed to render protection against l-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-neurotoxicity to a significant extent via a free radical scavenging mechanism, which is independent of its ability to inhibit monoamine oxidase-B (MAO-B) in the brain. We investigated the hydroxyl radical (.OH) scavenging action and neuroprotective effect of D-deprenyl, its less active isomer, in MPTP-induced dopaminergic neurotoxicity in mice to test whether the chemical structure of the molecule or its biological effects contribute to this property. To achieve this goal we studied the effects of D-deprenyl on: (1).OH production in a Fenton reaction; (2) MPTP-induced.OH generation and dopamine (DA) depletion in vivo, employing a sensitive HPLC-electrochemical procedure; and (3) formation of MPP(+) in vivo in the striatum following systemic administration of MPTP, employing an HPLC-photodiode array detection system. D-deprenyl inhibited ferrous citrate-induced.OH in vitro (0.45 microM) and MPTP-induced.OH in vivo in substantia nigra (SN) and in the striatum (1.0 mg/kg, i.p.). D-deprenyl did not, but L-deprenyl (0.5 mg/kg dose) did significantly inhibit formation of MPP(+) in the striatum 90 min following systemic MPTP injection. It failed to affect MAO-B activity at 0.5 mg/kg in the striatum, but effectively blocked MPTP-induced striatal DA depletion. The potency of D-deprenyl to scavenge MPTP-induced.OH in vivo and to render protection against the dopaminergic neurotoxicity without affecting dopamine turnover, MAO-B activity, or formation of MPP(+) in the brain indicates a direct involvement of.OH in the neurotoxic action of MPTP and antioxidant effect in the neuroprotective action of deprenyl.

 

 

 

 

http://www.ncbi.nlm..../pubmed/9387872

The effect of L-deprenyl, D-deprenyl and MDL72974 on mitochondrial respiration: a possible mechanism leading to an adaptive increase in superoxide dismutase activity.

L-Deprenyl is an irreversible monoamine oxidase-B inhibitor with a complex pharmacological profile. For instance, L-deprenyl administration to rat and mice increases cytosolic CuZn- and mitochondrial Mn-superoxide dismutase activities in the striatum. CuZn- and Mn-superoxide dismutase are enzymes involved in defense against superoxide (O2.) radicals. Hence, an increase in CuZn- and Mn-superoxide dismutase activities is suggestive of oxidative stress. The major intracellular site of O2. radicals formation is the mitochondrial respiratory chain. Several reports indicated that alterations in mitochondrial respiratory functions enhances O2. production. We observed that L-deprenyl induced a dose-dependent inhibition of oxygen (O2) consumption (state 3) during ATP synthesis in presence of complex I (pyruvate and malate) and complex II (succinate) substrates in fresh mitochondrial preparations. D-Deprenyl produced a similar inhibitory profile whereas MDL72974, a selective monoamine oxidase-B inhibitor, was less effective. Administration of D-deprenyl or MDL72974 to mice resulted in an increase in both striatal CuZn- and -Mn-superoxide dismutase activities. Accordingly, we propose that the impairment of mitochondrial respiratory functions which stimulates O2. formation could modulate CuZn- and Mn-superoxide dismutase activities, through a mechanism that appears to be independent of monoamine oxidase-B inhibition.

 

 

http://www.ncbi.nlm....les/PMC3695399/

 

Treatment of old female rats with both doses of L-deprenyl significantly (p<0.005) increased NE concentration while D-deprenyl had no effect on the age-related decrease in splenic NE concentration. There was a similar age-related reduction in NE content in the whole spleen of old female rats regardless of the treatment given (

 

^D-Deprenyl should have more of an effect on dopamine rather than norepinephrine. The L-metabolites on their own possess a greater affinity for NE rather than dopamine and the reverse is true for their dextrorotatory counterparts.

 

[FeelsNumbMan]

Selegiline/Rasagiline has been something I've had in my bucketlist for a while now.

 

I dunno the differences but I'd be willing to try it out.

[medievil]

Im interested

[Ultravioletbllc]

I'm in

[medievil]

Im interested

Dunno what state I was in but this buying in a group buy is the biggest waste of money ever, just buy dexamp and selegiline lol.

[medicineman]

dexamp isn't easy to obtain. where I live, having dexamp without a script could cost you a criminal record, and no jail sentence if I'm lucky.

I'm interested.

[FW900]

 

Im interested

Dunno what state I was in but this buying in a group buy is the biggest waste of money ever, just buy dexamp and selegiline lol.

 

 

Because the dextrotatory isomer of selegiline produces a host of different effects, largely unknown.

 

The catecholaminergic activity enhancer (CAE) effect of L-selegiline, is well known. Who is to say what catecholamines are effected? I'd be willing to bet L-selegiline is more partial toward norepinephrine, epinephrine, and trace amines rather than dopamine. I assume that D-selegiline, would lean more toward dopamine. According to Knoll this CAE effect does not come from the amphetamine metabolites despite amphetamine in low dosages acting as a CAE. If anyone will recall, BPAP's MoA was attributed to it's effect as a CAE.

 

 

D-Amphetamine: Dopaminergic (CNS stimulation)

D-selegiline: ?

 

L-Amphetamine: Norepinephrinergic (PNS stimulation)

L-Selegiline: ?

 

 

The small miniscule dosages would mean the effect of the amphetamine metabolites and exposure to them would be diminutive and in the nootropic range. Because D-selegiline would essentially serve as a prodrug, their delivery would be much more controlled and smoother than taking dextroamphetamine at once and have less abuse potential. Last I checked, both amphetamine and methamphetamine are illegal or are controlled substances in most countries.

 

Lastly, there are people who would rather minimize their exposure to the amphetamine metabolites via sublingual administration.

 

To recap:

• The MAO-B inhibition is less pronounced than L-selegiline
• Presumably different CAE-effects than L-selegiline
• Dextrotatory metabolites offer their own nootropic effects
• Metabolites are delivered in a controlled manner

All of these coalesce to make D-deprenyl a great candidate as both a nootropic and as a drug that could potentially treat ADHD. Comparing D-selegiline to of combination of L-selegiline with D-amphetamine is like comparing apples to oranges; they are completely different animals.

Edited by FW900, 16 July 2014 - 06:24 PM.

[chemicalambrosia]

Well said FW900. I can't believe this thread hasn't gotten more interest. I tend to think most people see the thread title and don't realize D-Deprenyl isn't the same thing as selegiline. Then, I'm guessing many that get beyond that point fail to go so far as to even skim through the full study linked to in the OP or read the abstracts you posted. This stuff has way more potential than the majority of the stuff that gets talked about around here.

To add, a quote from the study linked in the OP:

 

Second, the higher rates of self-administration for d-deprenyl than l-deprenyl may be the result of factors other than the production of active metabolites. One possible factor is inhibition of dopamine uptake. d-Deprenyl has been shown to be a potent inhibitor of dopamine uptake in the rat striatum, while l-deprenyl only weakly inhibits dopamine uptake (Fang and Yu 1994; Magyar et al. 2004). Thus, inhibition of dopamine uptake could also account for the observed differences in self-administration between d-deprenyl and l-deprenyl

 

 

[hypnotik]

I'm in on this.  I've been taking L-Dep on and off for a few years. D-Dep sounds promising.

[noot_in_the_sky]

I got a few questions:

 

1. Base on the first study by yadayada, it seem d-deprenyl has a bigger risk of been addictive, is this right?

    "These results indicate that d-deprenyl, but not l-deprenyl, may have abuse potential."

 

2. Is it going to be much more expensive then the L form?

 

3. Will it bee a good idea to comine L-deprenyl + D-deprenyl or D-deprenyl + BPAP?

 

4. It seem D-deprenyl is better for nootropic, but which one is better for PD, antiaging, and mood?

Edited by noot_in_the_sky, 22 July 2014 - 02:15 PM.

[Ultravioletbllc]

D deprenyl has an amazing potential for abuse that's why it's not being produced , a prodrug of three re-active dopaminergic agonist/protective/substrate compounds

I think it will be the "fix" for ADHD-PI I have no idea at what dosage
However bpap+d-dep sounds amazing
As deprenyl orally with sublingual (-)-bpap created the most synergies with selegiline I've ever experienced

[FW900]

I got a few questions:

 

1. Base on the first study by yadayada, it seem d-deprenyl has a bigger risk of been addictive, is this right?

    "These results indicate that d-deprenyl, but not l-deprenyl, may have abuse potential."

 

2. Is it going to be much more expensive then the L form?

 

3. Will it bee a good idea to comine L-deprenyl + D-deprenyl or D-deprenyl + BPAP?

 

4. It seem D-deprenyl is better for nootropic, but which one is better for PD, antiaging, and mood?

 

1. Almost any psychostimulant has abusive potential. This is nothing to be afraid over-- if this ever does come to market, most users will be taking it in low dosages. Many people take substances (e.g, methylphenidate, amphetamine) that have abuse potential in therapeutic dosages without becoming addicted. Furthermore, it acts as a prodrug to the amphetamine metabolites, meaning you cannot use a faster route of administration for the sake of producing a euphoric effect. Additionally, sublingual administration will reduce the abuse potential by reducing the number of amphetamine metabolites. The abuse potential, outside of the amphetamine metabolites, seem to come from the fact that d-deprenyl acts as a DRI.

 

The previous poster, Ultravioletbllc, is incorrect. The reason it is not available is because this drug was originally used for parkinson's disease, and l-deprenyl is a more potent MAO-B-I which is more useful when paired with other things (levodopa for instance). There are substances that are even stronger candidates for abuse that are still produced.

 

The human equivalent dose in the studies with abuse potential, would be very high. Correct me if I'm wrong but on the high end 3mg/kg for squirrel monkeys translates to a human dose equivalence of 0.973 mg/kg, which is extremely high. 10x higher than the typical human dose.

 

2. Synthesized or compared to existing prices of l-deprenyl? They will cost roughly the same price to synthesize; the only difference is the end enantiomer. Existing L-Deprenyl is exponentally cheaper due to it's widespread use.

 

3. I would be cautious with this combination but it really would not be that bad. The only danger I see is a stronger potentiation of the amphetamine metabolites due l-deprenyl being a stronger MAO-B inhibitor.

 

4. It is difficult to say. There is research showing that l-deprenyl is effective for PD treatment and has been used in life-extension experiments with rats. Sublingual administration, L-deprenyl is probably better for life extention due to the fact that d-deprenyl acts as a DRI; the sublingual administration would reduce the negative parasympathetic effects of the levoamphetamine metabolites of l-deprenyl which are probably detrimental to life extention.

[Ultravioletbllc]

I was unaware that they had trialed the d isomer at all

I wasn't trying to be a fear monger I'm just saying with what I've seen as far as what people will abuse , the potential is there

I'm highly interested for long term use for ADHD
And I agree whole heartedly with what you said in respect too methylphenidate and mixed amphetamine salts (adderall )

[Ultravioletbllc]

But I am uber excited about the promise this D ISO form could hold! Now let's get this thing going in a Tangible fashion , first off how many of us know a chemical supplier who we can contact about a custom synth ?

I'm gonna email the only People I know in the continental US who can do it better yet would so it ........

Let's see what the suppliers think?

But we need too figure out how much we want for our initial order.....
As well as how much the product is so we can figure out a denomination too get you in the door and a weight corresponding with the minimum group buy "buy-in" (initial investment)

Now I also think it would be very wise too start posting about d deprenyl at the only
Other relevant spots around on the net

And we need too contact a couple of the more experimental nootropic substance /life enhancement chemical suppliers
And see if we can't coax someone with more investment Capitol too just get a custom synth done , especially with the demand

Someone who knows the guys over at ceretropic should really contact them ......


I will contact our friends over at THT and see what they have too say

Out of all the suppliers these two seem most likely too be able too get this thing on it's feet , and I wouldn't be surprised if this is already on ceretropics list of future products ......l.




Let's start making this thing come too fruition !

[Reformed-Redan]

Anyone found a supplier?

[medicineman]

Maybe teamtlr can carry it if there's enough interest!

Edited by medicineman, 27 July 2014 - 05:50 PM.

[noot_in_the_sky]

TeamTlr, are they good? I taught many people where complaining about them.

 

Anyway, if a company is welling to carry it I'll try it. Personally I'm more intrested in longevity, and it seems that the levo form is better for this.  Nonetheless, I'm still intrested in giving this compound a try at least once.

[joeyo]

yes please. w/ 5-10mg l-deprenyl daily I notice GI tract disturbances (bloating, gas) in the pm. I wonder if d-deprenyl dosing would run absent of said side effects..

 

I plan to look into synth. routes- appears quite easy at a glance

[Sciencyst]

There is no way this will end well. This is playing with fire..

[chemicalambrosia]

There is no way this will end well. This is playing with fire..

 

Some of us have been pyromaniacs since we were kids. Eyebrows grow back.

[Sciencyst]

Im not worried about the pyromaniacs... Im worried about the non-pyromaniacs who will catch on and spread it until its plastered all over good morning america.

D deprenyl WILL be habit forming and it WILL spread. No doubt about it.


... I suppose I am over reacting a bit, and I cant stop this from happening, but it would at least be nice for people to educate themselves before messing with this, and itd be even nicer if it is not marketed aggressively or at all.


.......... One could say it would be a prodrug like vyvanse, but it should be active before metabolism. And indeed its metabolites are present in such minute quantities that they shouldnt be a huge issue. Honestly, I would love to give this a try for potential nootropic effects, but it needs to be respected, especially so before we know more about it, experientially. Even if it ends up not being abusable and having an awesome safety profile with low habituation, getting it will br difficult in the first place. Synthesis requires D-METHAMP as an intermediate. So ones best bet is asking ones local walter white to throw a propargyl group on his product lol

Edited by katuskoti, 30 July 2014 - 03:28 AM.

[FW900]

Im not worried about the pyromaniacs... Im worried about the non-pyromaniacs who will catch on and spread it until its plastered all over good morning america.

D deprenyl WILL be habit forming and it WILL spread. No doubt about it.

 

Which aspect of habit formation scares you? (1) The dextrorotatory amphetamine metabolites? Or, (2) the DRI effect?

 

 

(1) Let me reiterate; D-deprenyl is a prodrug. You need to take a prodrug orally and have it undergo first-pass hepatic metabolism before anything happens, so the amphetamine metabolite abuse potential is extremely low. Abused amphetamines and stimulants are frequently insufflated/smoked/injected/rectally administered in absurdly high dosages, (these RoAs bypass first-pass metabolism) for a "rush" or quick onset of a euphoria. Any of these routes of administration will ultimately be useless for a prodrug and will not result in a quicker onset of effects with a prodrug. Lastly, a prodrug is slowly metabolized (e.g., Vyvanse) , meaning if you take a larger amount of it at once, it will take a while before it is hydrolyzed/catalyzed into the amphetamine metabolites.

 

Quite a headache to abuse it for the amphetamines.

 

(2) If the DRI effect was extremely pronounced, it would have likely caused PNS stimulation (elevated heart rate/BP) and there is no evidence of this. This leads me to believe that the DRI effect of it is minimal and is possibly selective to very specific dopamine subtypes (D1, D2, ect).

 

Amfonelic Acid is 50x more potent than Methylphenidate and does not make the news.

 

 

In comparison to other drugs, even legal ones, D-deprenyl looks like a major hassle and headache to deal with and likely would not even make a web story on a news site let alone Good Morning America.

[Sciencyst]

I admit defeat. Mine was a fear based knee jerk reaction to such a perfect compound. Honestly... dexedrine has helped me more than any psychiatric medicine I have tried, and I would kindly welcome a more dopaminergic noot with little PNS effects. Heavily (nor)epinephrine affecting things mess with me the most