deprenyl and related chems...

loki · guinea pig

I have recently become very interested in a close relative of methedrine, deprenyl.

deprenyl molecular diagram at chemfinder

Apparently the D isomer, like it's close relative, is more potent. I thought about whether one could get analogous activity from a different N substituent than the propargyl but the propyl substituent has been tested and while it has similar 'catecholamine enhancement activity', it lacks the MAO-B inhibition effect. The MAO-B inhibition effect is responsible for the reduction of free radical damage that makes it an effective treatment for parkinson's disease. However I am inclined to think that this is a limited view of the potential of this drug and pharmacologically related compounds. I was startled to learn that nicotine shares some of these effects, and brahmi (bacopa monniera) also (I intend to try out deprenyl in combination with gingko, nicotine, brahmi and phenylalanine soon- although i am a little concerned that gingko has MAO-A activity)

It rather seems to me that D-Deprenyl would be a superior drug to methedrine because of its reduction of the decomposition of, in particular, phenethylamine, but dopamine as well, and possibly the dopamine agonism effect of the D isomer is why it has not been very much talked about.

What I am interested in is developing methods to synthesise either chiral or racemic deprenyl, and seeing that it is so similar to methedrine, i should think that it would not be hard to do, the only difficulty I see is to do with that propargyl radical. I would think that, having limited uses and the primary drug it is connected with being deprenyl, that it would not be watched or terribly hard to aquire - well, from a search of chemfinder, it seems that the propargyl chloride would be the most likely one to pick.

Obviously P2P is the first thing one has to acquire, but in this case, the propargyl radical is probably the more challenging one, to be able to synthesise it would be the ideal situation.

One thing to note about deprenyl is that it is known to diminish the activity of methedrine. Regardless of this, I think that it is a very worthwhile avenue of investigation, as free radical damage is one of the big problems with methedrine, and deprenyl would be a good way to protect against this damage, and in itself, may be a suitable substitute for methedrine in many ways, and as luck would have it, the activity of deprenyl is in the same range as methedrine and so as an end point from starting with p2p is not an un-economic goal.

In case you are wondering what I am intending to put forth in this post, what I am mainly intending to do is raise the topic so that people can consider it. It is my feeling that this drug, and related drugs, could be viable and much more physiologically benign than methedrine. Combining D,L deprenyl with 500mg of phenylalanine is a very probable substitute for methedrine and would ultimately have positive benefits for people using it. I personally have been very attracted to methedrine because of the way it improves my mental function, but I don't like the downsides of it. I know in terms of commercial production it doesn't make sense to make pills of D,L deprenyl and L phenylalanine, but from a perspective of having one's cake and eating it too, when it comes to dopamine elevation drugs, I am not aware of much else that compares, and in moderate doses combined with a phenethylamine precursor (or phenethylamine itself) would be difficult to distinguish from ---- except for the lack of degradation afterwards.

So, my intent in starting this thread is to stimulate a discussion about economic and viable clandestine routes to synthesising this drug. I am keen to hear about routes to the propargyl radical.

joe_aldehyde · huxleys associate

http://www.selegiline.com/synthesis/index.html

Senfgas · Thu May 26, 2005 9:53 pm

Could you be so kind and provide reference for the synthesis steps in your link?

thank.s

joe_aldehyde · huxleys associate

i'm sorry i don't have any, i just linked there because i knew the synthesis was on that site. it seems the correct path to me, though. the exact conditions will only be revealed if someone can retrieve a related paper, which i cannot. but you can also buy selegiline relatively cheap on the net. and it's not fake, i tried it. it's active in the region of 0.5-1.0mg. i actually made the mistake and took amitriptyline 1 week after the last administration of selegiline which led to a very mild serotonine syndrome. i guess indoleamine will step right in and call me an idiot again, but hey! you have been warned. don't take that stuff together (2 weeks pause minimum) with any drugs that affect your neurotransmitter release and reuptake, or you could die. i can't because i'm son of earth Wink

loki · guinea pig

yeah it is pretty easy to get online, but it could be a bit cheaper imho

it's got studies saying it's good for depression, a doctor with half a brain who knows you can't take ssri's, maoi's and tricyclics because it gives you mild serotonin syndrome or anticholinergic effects would be able to get it for you on prescription (that's how i'm getting it, i really can't take all those other drugs they all make me sick, and even the prescription stims, ritalin and amphetamine, do bad things to me). hell, just say you don't want to take those other ones.

btw, the dose for the average person (well, 20-30something male) is 2.5-10mg (kroll, the dude who invented it says that as you get older you need less as a male, females are the opposite)

joe_aldehyde · huxleys associate

i'm sorry i don't get what you are trying to say.

primathon · modified

Electroencephalopod · Sat Jun 25, 2005 1:07 pm

Personally I have found through Ye Olde Gullet Test that arguably the best cholinosterase inhibitor available is idebenone. Gentle and without overly-stimulating properties, it focuses the beta range of the EEG like a laser. Useful for soaking up school and all its droll malcontents.

$0.02.

joe_aldehyde · huxleys associate

can you post more info about the compound you're talking about, mr. Pod?

loki · guinea pig

to elaborate more: a friend passed this pdf onto me: https://m0c.no-ip.org/asymmetric_selegiline.pdf

It shows a reaction which proceeds through l-desoxyephedrine amusingly enough, as follows:

L alpha, beta dihydroxy phenyl propane + thionyl chloride + triethylamine at 0`C 85% yield
with above product + sodium azide in acetone/water at 80`C 82% yield
L beta-amino alpha hydroxy phenylpropane + triphenyl phosphate + nitroethane 90% yield --> methyl phenyl aziridine
methyl phenyl aziridine + palladium on carbon + ammonium formate in MeOH reflux 88% yield --> l-desoxyephedrine
l-desoxyephedrine + propargyl bromide + potassium bicarbonate + nitroethane rt to 80`C 72%-80%

sorry if that's a bit weird, i just kinda translated it from the abbrieviated code it is in the pdf. just wanted to list the methods and chems used... look at all that lovely but difficult to get nitroethane used :'( well anyway. it did give me food for thought. one thing was the use of methylphenylaziridine as a route to desoxyephedrine (made by means other than the usual ephedrine, looks like it could be done on an amine with the opposite positioning of the hydroxyl and amine than is found on ephedrine).

any suggestions for alternatives to the nitroethane/K2CO3 or LAH reduction to transform D-desoxyephedrine into D-selegiline would be very much appreciated. looks like nearly anything would do it.

D selegiline sounds like a very worthwhile subject of study for amphetamine analogs - they use the magic words 'abuse potential' everywhere i read references to the D isomer and that instantly implies that it's fun. the L isomer is too potent as a mao-b inhibitor to be able to have any fun with it at all, but it combines terribly well with desoxyephedrine (smooths out the crinkles) - thus, logically speaking, the D isomer of selegiline would be like that combination but safer, less mao-b inhibition per unit of fun.

Electroencephalopod · Sat Jul 02, 2005 2:10 am

http://internaf.org/ataxia/Idebenone_desc.html

A little vignette on my personal use of idebenone. It is legal to buy in the US from other countries in 3-month supplies or less. Thanks to good ole' Senile Fascist Uncle Sam, this is a rathr ambiguous law. Suffice to say it is not well enforced. I've ordered several times from sources in Canada (get 'em while you can) and the UK and have never had a problem with them being seized by customs.

Typically I will use idebenone for a one-month period with a one month rest period in between. I have noticed several distinct improvements:

My ability to remember things, including minute details, is greatly enhanced. In this sense I used it every day for six months in a particularly intense portion of school. It helped incomparably.

My ability to articulate my thoughts into words also improved greatly.

My general mood was both improved and more stable with the use of idebenone. According to the literature this is because it up-regulates production of serotonin.

I had previously tried several other so-called 'nootropics' including deprenyl, piracetam and huperzine a. I found all of these too 'stimulating' to varying degrees. What I was looking for - increased fluidity and accuracy of thought, balanced mood and a general focused demeanor without an overly stimulating effect, I found in idebenone hands down.

OK this might have sounded slightly preachy, but I assure anyone reading this that I am NOT some sort of pundit for a company that makes idebenone. I'm simply a neuronaut who found what works for him. Just my $0.02. Your mileage may vary.

Oh, and P.S.: Idebenone in a standard dose combines very well with psilocybe mushrooms. Emphasis on the very. =)

joe_aldehyde · huxleys associate

whats the price you get? i only saw it for like 500$ per kilo while it said you need like 1-5g per day? whats your dosage? some more details please - and less preaching Wink

loki · guinea pig

i actually need something more stimulating than L-deprenyl... so, as they say, different strokes.