![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 34 to 58 of 58. Go back in thread:
Posted by bulldog2 on May 3, 2008, at 18:08:12
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by undopaminergic on May 3, 2008, at 11:20:59
I think it's the elevation of pea that gives selegiline an AD response..So maybe low dose pea or l-phenyalanine which converts to pea or partly to pea..there are various forms of phenylalaine and there are various claims of which converts to pea. the d and dl forms have various claims.
Posted by bulldog2 on May 3, 2008, at 18:23:04
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by bulldog2 on May 3, 2008, at 18:08:12
Wonder how much sublingual you need to inhibit mao-a? Also at that dose would you need to follow the diet since the absorption is bypassing the stomach.
Posted by Ezekiel on May 4, 2008, at 4:22:48
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by bulldog2 on May 3, 2008, at 18:23:04
Great commentary on the perennial Cytrate vs. HCL debate everybody! Also, thanks alucard for elucidating chemical principles for the rest of us non-specialists, I took one pharmacology & inorganic chem class in college, so I know just enough to be dangerous! I've been fixated on this debate for 2 weeks ever since I decided to try deprenyl & began researching it earnestly, as a result of reading over this thread I feel like I understand the issues a little more objectively now. Ok now back to the point of my post.
Hopefully my question for you all isn't to much of a digression: i.e., is there a big difference in AD/motivational efficacy if one ingests deprenyl tabs (I just ordered some generic tabs) vs. subligual liquid under the tongue? Does the liquid possess a greater AD effect (or just greater any effect!) via the liquid route due to directly entering circulation w/o undergoing any first pass breakdown in the liver?
If someone has experience with both modes of deprenyl delivery and would be willing to enlighten me, well then that would just be faaaaaantastic :=]
Posted by Alucard on May 4, 2008, at 15:16:10
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Ezekiel on May 4, 2008, at 4:22:48
Ezekiel - I don't have experience with both forms, or even much personal experience with the form I'm taking, but I did research other people's opinions pretty heavily and the gist of what I got about liquid vs. pill was that it pretty much depends on the individual. Some people strongly preferred the liquid, but a few said the pill form was definitely more effective for them. Since you've got the pills, just make sure to always take them with a meal that's got a decent amount of fat in it because that increases bioavailability by a factor of 3 - 4 times, a huge difference for getting your money's worth. For motivational/antidepressant purposes (the same reason I'm taking the stuff) you might want to take some phenylalanine or tyrosine (NOT tyramine) with it, or maybe a Mucuna pruriens extract. That's just educated speculation on my part, however, and a big thing to keep in mind on this forum seems to be: "Your mileage may vary".
Something to keep an eye out for: the first week or so that I was taking the liquid, I felt a pretty strong urge to do some serious napping around 1pm-2pm daily. I indulged (I'm in the tropics where a lot of people do that anyway) and it felt incredibly refreshing and by the second week I had "recharged the batteries" enough that I didn't feel like napping any more. Maybe the deprenyl allowed my body to demand the rest it needed? Or maybe it wasn't related to the deprenyl at all, but if the same thing happens to you, give it a week or two before deciding that it's the exact opposite of motivational.
Good luck buddy! I'll post here when I start the Mucuna pruriens extract and have a better personal feel of how well it works for amotivational depression. You be sure to let us know how the pill form works out for you, yea?
Related questions: Anybody have personal experience with L-phenylalanine vs. the racemic DL form (DLPA)? I've read the opinions of many people who swear that only the L form by itself works, but just as many who swear that DLPA is far more effective for our purposes. And what about skipping the phenylalanine and going straight to the L-tyrosine? Or both? Thoughts anyone?
Posted by bulldog2 on May 4, 2008, at 16:45:35
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Alucard on May 4, 2008, at 15:16:10
> Ezekiel - I don't have experience with both forms, or even much personal experience with the form I'm taking, but I did research other people's opinions pretty heavily and the gist of what I got about liquid vs. pill was that it pretty much depends on the individual. Some people strongly preferred the liquid, but a few said the pill form was definitely more effective for them. Since you've got the pills, just make sure to always take them with a meal that's got a decent amount of fat in it because that increases bioavailability by a factor of 3 - 4 times, a huge difference for getting your money's worth. For motivational/antidepressant purposes (the same reason I'm taking the stuff) you might want to take some phenylalanine or tyrosine (NOT tyramine) with it, or maybe a Mucuna pruriens extract. That's just educated speculation on my part, however, and a big thing to keep in mind on this forum seems to be: "Your mileage may vary".
>
> Something to keep an eye out for: the first week or so that I was taking the liquid, I felt a pretty strong urge to do some serious napping around 1pm-2pm daily. I indulged (I'm in the tropics where a lot of people do that anyway) and it felt incredibly refreshing and by the second week I had "recharged the batteries" enough that I didn't feel like napping any more. Maybe the deprenyl allowed my body to demand the rest it needed? Or maybe it wasn't related to the deprenyl at all, but if the same thing happens to you, give it a week or two before deciding that it's the exact opposite of motivational.
>
> Good luck buddy! I'll post here when I start the Mucuna pruriens extract and have a better personal feel of how well it works for amotivational depression. You be sure to let us know how the pill form works out for you, yea?
>
> Related questions: Anybody have personal experience with L-phenylalanine vs. the racemic DL form (DLPA)? I've read the opinions of many people who swear that only the L form by itself works, but just as many who swear that DLPA is far more effective for our purposes. And what about skipping the phenylalanine and going straight to the L-tyrosine? Or both? Thoughts anyone?what dose of the liquid were you doing? I would think with the sublingual it would be easier to get mao-a inhibtion than with the pills..Maybe like emsam without dietary restrictions at low doses. I wouldn't use tyrosine as it basically becomes ne and da. The phenylalanine gives you pea also which is good for depression. Some have used pea straight at low doses with selegiline. But you have to make sure you don't get into high doses and get blood pressure spikes.
Posted by undopaminergic on May 4, 2008, at 21:36:34
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Alucard on May 4, 2008, at 15:16:10
> just make sure to always take them with a meal that's got a decent amount of fat in it because that increases bioavailability by a factor of 3 - 4 times, a huge difference for getting your money's worth.
>That does increase the bioavailability of selegiline itself, but it has the opposite effect as far as the metabolites are concerned. The reason why some people find ingestion to be more effective than sublingual absorption may be the metabolism of selegiline to L-methamphetamine and L-amphetamine in the liver. With regard to neuroprotection, the formation of desmethylselegiline is also of relevance.
I would be very interested in learning about comparative experiences with selegiline and the other selective MAO-B inhibitor, rasagiline, which does not give rise to amphetamine metabolites - this would help clarify the relative roles of the different chemical entities.
> For motivational/antidepressant purposes (the same reason I'm taking the stuff) you might want to take some phenylalanine or tyrosine (NOT tyramine) with it, or maybe a Mucuna pruriens extract. That's just educated speculation on my part, however, and a big thing to keep in mind on this forum seems to be: "Your mileage may vary".
>
> Related questions: Anybody have personal experience with L-phenylalanine vs. the racemic DL form (DLPA)? I've read the opinions of many people who swear that only the L form by itself works, but just as many who swear that DLPA is far more effective for our purposes. And what about skipping the phenylalanine and going straight to the L-tyrosine? Or both? Thoughts anyone?
>The reason for using L- or D,L-phenylalanine rather than tyrosine or L-dopa (including Mucuna pruriens) is that it serves as a precursor to phenylethylamine (PEA). PEA is the preferred substrate of MAO-B, which selegiline inhibits, and is similar to amphetamine in its pharmacological actions: it releases dopamine (DA) and noradrenaline (NA) from storage vesicles into the cytoplasm, and reverses the direction of the DA and NA transporters, resulting in the massive efflux of the neurotransmitters into the synaptic cleft. Unless one has advanced Parkinson's disease, the effect of PEA on synaptic DA concentrations is far more substantial than that of L-dopa or other DA precursors. D-phenylalanine is more effective as a PEA precursor than the L-isomer as it is not subject to hydroxylation (to tyrosine), but personally, I found both inadequate, and had to resort to using PEA directly.
Eventually, I found the use of PEA and selegiline not to be very productive. Alternatives that I've since taken up in preference include methylphenidate, modafinil, memantine and some amisulpride or sulpiride.
Posted by Amigan on May 5, 2008, at 1:45:03
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by undopaminergic on May 4, 2008, at 21:36:34
> > just make sure to always take them with a meal that's got a decent amount of fat in it because that increases bioavailability by a factor of 3 - 4 times, a huge difference for getting your money's worth.
> >
>
> That does increase the bioavailability of selegiline itself, but it has the opposite effect as far as the metabolites are concerned. The reason why some people find ingestion to be more effective than sublingual absorption may be the metabolism of selegiline to L-methamphetamine and L-amphetamine in the liver. With regard to neuroprotection, the formation of desmethylselegiline is also of relevance.So, you get more metabolites in your system if you ingest selegiline on an empty stomach? Interesting! I used to think that both the bio-availability of selegiline AND its metabolites increases with food. Thanks for the information!
I'm one of the few people who finds the oral route to be more effective. I'll try to ingest it without food and see what happens.
Posted by undopaminergic on May 5, 2008, at 9:31:23
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Amigan on May 5, 2008, at 1:45:03
> > > just make sure to always take them with a meal that's got a decent amount of fat in it because that increases bioavailability by a factor of 3 - 4 times, a huge difference for getting your money's worth.
> > >
> >
> > That does increase the bioavailability of selegiline itself, but it has the opposite effect as far as the metabolites are concerned. The reason why some people find ingestion to be more effective than sublingual absorption may be the metabolism of selegiline to L-methamphetamine and L-amphetamine in the liver. With regard to neuroprotection, the formation of desmethylselegiline is also of relevance.
>
> So, you get more metabolites in your system if you ingest selegiline on an empty stomach? Interesting! I used to think that both the bio-availability of selegiline AND its metabolites increases with food. Thanks for the information!
> I'm one of the few people who finds the oral route to be more effective. I'll try to ingest it without food and see what happens.
>I just tried to verify that my recollection of selegiline pharmacokinetics was correct, but I can't find any references confirming increased bioavailability of the metabolites when selegiline is taken without food; one study suggests that the metabolites are unaffected by coadministration with food, whereas the bioavailability of selegiline is increased. Anyway, it still seems plausible that the increased metabolism of selegiline when taken on an empty stomach would increase production of the metabolites.
Posted by alucard on May 6, 2008, at 17:22:37
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by undopaminergic on May 5, 2008, at 9:31:23
>the increased metabolism of selegiline when taken on an empty stomach would increase production of the metabolites.
That makes more sense to me too. Bioavailability = absorption of the primary molecule (selegiline in this case), and since breakdown metabolism happens after absorption it only makes sense that starting with more would lead to more, not less, of the end products. Perhaps the article you read stated that the RATIO of selegiline to its metabolites was lower when taken on an empty stomach? So there would be less selegiline RELATIVE to its metabolites when taken with food, but more of both selegiline and the metabolites overall.
Incidentally, with the liquid sublingual form I haven't noticed a difference with vs. without food, so I just take it with as clean a mouth as possible (i.e. I brush my teeth, rinse with water a few times, then wait 5 minutes and put the drops in), same concept as cleaning the skin on an area where you're going to use a dermal patch.
Posted by Alucard on July 3, 2008, at 17:49:10
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by alucard on May 6, 2008, at 17:22:37
Selepryl has definitely turned out to be more effective, and refrigeration seems to make it work better as well (but maybe that's only true for extremely hot/humid climates like where I live, since refrigerators dry things out in addition to cooling them down)
That's my personal opinion, and so far as effectiveness for depression goes?
3 drops Selepryl in the morning with 1 or 2 Mucuna Pruriens extract pills (~60mg of L-dopa in each) at least an hour before any food and then late in the afternoon, at least 2 hours after a meal and 1 hour before the next meal I take 1 or 2 500mg L-Tryptophan pills. Works wonders for my motivation, sleep, patience, energy, and overall happiness and enjoyment of life.
Aloha, enjoy yourselves kids!
Posted by GarbageMan on December 18, 2008, at 4:04:28
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by alucard on May 6, 2008, at 17:22:37
I can tell you from first hand experience that I prefer liquid selegiline citrate over any of the alternative forms. Over a period of four years I've taken HCL, EMSAM and Zelepar(sublingual tabs that dissolve under your mouth). EMSAM is far too potent for me and actually makes me feel rather tired. Zelepar is very nice but given that LSC exists, it's neither worth the expense nor the hassle to achieve the product from a doctor. HCL works great as well but is mild in terms of positive effects by comparison.
I'm currently taking Cyprenil and I love this tonic so if you're tossed between which tonic to go with, Cyprenil is 'good enough'. Within thirty minutes(often much quicker)of placing LSC under my tongue, I feel rather invigorated. There is a very pleasing and mild euphoria that takes over. My thoughts become much clearer and calculating. I feel energized to take on intellectual tasks: reading and writing in particular. This is somewhat hilarious given that I deliver garbage for a living.
I'll often sit at my kitchen table and write short stories about my past life for hours on end after work. Why? For who? I'm not sure really. I don't plan on publishing them. It simply relaxes me to put words onto paper now. Who would want to read about a garbage man anyways?
It's all rather amusing b/c my wife will stand there looking at me from afar, frustrated, wondering why I'm not watching the usual sitcoms with her like I used to.
Frankly I'm not in the least bit bothered by the fact that she's upset with me b/c I'm completely absorbed in my own thoughts. Verbal fluidity is markedly pronounced as words seem to flow from my mouth like a knife slicing through butter. (I laugh at my usage of these phrases such as markedly pronounced and verbal fluidity and even my lame attempt at a simile haahahha)
If you knew me, you would be laughing with me. Like I said, I'm a garbage man and I'm certainly not the type of person that says 'markedly pronounced' or that says 'certainly' for that matter or 'for that matter'.
I'm not an intellectual at all. I've read very little in my life. If weren't first selegiline, I probably wouldn't even know who the current President of the United States is. I never even bothered to make it through college. Although I had always told myself that I should read and study but I never quite seemed to gather the mental energy required to do so.
Writer??? HAH!! The notion of me writing at the kitchen table in my garbage covered overalls is seemingly ridiculous. Yet upon taking a single drop of LSC, I feel compelled to express my thoughts for hours at a time. I've written over forty short stories since taking selegiline which I've been on and off of for four years now. I suppose I've always wanted to write but, akin to reading, the mental energy to do so was never quite there.
Perhaps you're wondering how a lowly garbage man such as myself even came across an exotic drug like selegiline. That's a fairly long story but about four years ago, I was having sexually related issues and finally gathered the nerve to see a doctor about them. After a few sessions he prescribed selegiline HCL 2.5mg bid.
Which brings me to perhaps the most significant aspect of selegiline. After approx an hour or so a taking LSC, I notice a pronounced increase in my libido. Everything in the sexual arena seemed to be intensify; even my ability to fantasize.
At present, when I bother to break myself away from my intellectual pursuits and tend to my wife's sexual needs, my wife has never been more pleased. Our sex life has never been better. I actually feel like a man again. Not a garbage man.
But there is yet one more seemingly miraculous result that I've received from this tonic. It seems to build muscle. Which make me wonder, is this stuff going to increase the size of my endowment as well??
I'm nothing close to a body builder(5'11 and 175 lbs as of six months ago). I've recently started to experiment with lifting weights. Not sure why? I just felt the need to workout similar to how I felt the need to write.
I've noticed rapid increases in strength. Normally I would only be able to bench press 160 lbs at maximum exertion--and that was ten years ago. However, after a few days of taking LSC, I was able to bench 215 lbs with ease. I can now bench 345 lbs after six months of regular working out. I can't believe it? Even my wife has been commenting on my physique and has been wondering where the hell my abdominals are coming from? She keeps remarking, "Are you sure you're not taking steroids?". I'm actually starting to look like I might be.
I've also been measuring my body fat for about six months as a means of documenting physical proof of what I'm experiencing. My body fat has gone from from 15% to 8%. After a month it was down to 13%. After two months down to 10%. After six months, 8% and it seems to have stabilized there.
Perhaps you're thinking this is simply from not eating as much--which is true, there is a degree of appetite suppression from LSC--however I'm fifteen pounds heavier. As of this morning, I way 190 lbs with 8% body fat. That's more than 15 lbs of muscle in six months. How is that possible when most of my exercise is composed of cardio while I only spend about 20 minutes, 3 times a week, lifting weights. I definitely don't have good genetics either. I mean I've never 'really' lifted anything but garbage cans before. Now I'm in the gym every day.
So i ask this question as a lowly garbage man who knows nothing about biochemistry except what he can scrape up from the Internet, "Is there some sort of direct correlation between dopamine and testosterone?" B/c I honestly feel like I'm sixteen again after four years of taking this stuff.
Much of the effect which I've been describing is the only reason I've ever even stopped. I seem to become a completely different person both physically and mentally. For example, I'm not the type of person that would ever share his thoughts communally like this in an open forum for others to read. Yet for some reason I feel very little inhibition. Almost none in fact. Fear seems to have subsided from my life. Is that good or bad? It hasn't gotten me into any trouble so I don't see it as a particularly negative thing. But how is that possible? I mean how is it that more people don't know about selegiline or am I just a freak case? If it really does what I'm claiming, you would think it would be fairly widespread. Right? Well that's my story. A bit long winded but you can't go wrong with the liquid stuff.
Posted by desolationrower on December 18, 2008, at 11:51:45
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s » alucard, posted by GarbageMan on December 18, 2008, at 4:04:28
Deprenyl didn't work as an antidepressant for me, but i did find it to be a positive overall experience. Sounds like it is really working for you. Its really quite a good tonic, I think its the kind of thing that just about everyone should consider taking to not only protect brain function against aging but also for the immediate benefits on libido and energy. Its great to hear someone who has gotten more out of life because of something like this.
-d/r
Posted by karl on December 18, 2008, at 21:24:42
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s » alucard, posted by GarbageMan on December 18, 2008, at 4:04:28
does dr. bob delete obvious advertisements like this?
Posted by karl on December 18, 2008, at 22:16:45
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s » alucard, posted by GarbageMan on December 18, 2008, at 4:04:28
and if he's going to allow obvious advertisements, people going for the 'mao-b inhibition' in selegiline should know that:
after four days, "inhibition of platelet MAO-B activity is approximately 95% after a daily dose of 2.5 mg selegiline [ORAL, HYDROCHLORIDE], whereas it takes only 48 hours (two doses) for doses of 5 mg and 7.5 mg to achieve this degree of inhibition." [parentheses mine]
any selegiline that reaches the bloodstream is metabolized by the liver into methamphetamine. much more selegiline is ABSORBED into the bloodstream sublingually [under the tongue] than orally [in the stomach, small intestine]. the reason selegiline [any form] is more invigorating under the tongue, therefore, is that MORE of it is metabolized into methamphetamine, and more quickly.
Posted by desolationrower on December 19, 2008, at 2:12:26
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by karl on December 18, 2008, at 22:16:45
> and if he's going to allow obvious advertisements, people going for the 'mao-b inhibition' in selegiline should know that:
>
> after four days, "inhibition of platelet MAO-B activity is approximately 95% after a daily dose of 2.5 mg selegiline [ORAL, HYDROCHLORIDE], whereas it takes only 48 hours (two doses) for doses of 5 mg and 7.5 mg to achieve this degree of inhibition." [parentheses mine]
>
> source: http://www.ncbi.nlm.nih.gov/pubmed/9853994?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
>
> any selegiline that reaches the bloodstream is metabolized by the liver into methamphetamine. much more selegiline is ABSORBED into the bloodstream sublingually [under the tongue] than orally [in the stomach, small intestine]. the reason selegiline [any form] is more invigorating under the tongue, therefore, is that MORE of it is metabolized into methamphetamine, and more quickly.When nutrients are absorbed from the intesting, they go directly to the liver via the portal vein. This is 'first pass metabolism.' Drugs entering otherwise may circulate w/o reaching the liver for a period of time. This is why oral drugs are more extensively metabolised before reaching the brain than otherwise administered drugs.
-d/r
Posted by karl on December 19, 2008, at 11:12:48
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by desolationrower on December 19, 2008, at 2:12:26
my mistake. too bad i can't delete MY post.
but people interested in the mao-b inhibition from selegiline should still know that it only takes a little bit to get near-full inhibition, and you can take it orally. at least according to the study i cited.
i'm curious: how many of you interested in the subject got the idea that mao-b inhibition would be helpful from david pearce's "Good Drug Guide"? he's real hot on selegiline even though he doesn't appear to be selling it [like he is knock-off amineptine].
anyone thinking of plunking down $1500 for 6 months of that stuff would probably be better served begging a generic ritalin prescription from their psych. $20 a month in my area.
Posted by desolationrower on December 19, 2008, at 13:39:59
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by karl on December 19, 2008, at 11:12:48
> my mistake. too bad i can't delete MY post.
>
> but people interested in the mao-b inhibition from selegiline should still know that it only takes a little bit to get near-full inhibition, and you can take it orally. at least according to the study i cited.
>
> i'm curious: how many of you interested in the subject got the idea that mao-b inhibition would be helpful from david pearce's "Good Drug Guide"? he's real hot on selegiline even though he doesn't appear to be selling it [like he is knock-off amineptine].
>
> anyone thinking of plunking down $1500 for 6 months of that stuff would probably be better served begging a generic ritalin prescription from their psych. $20 a month in my area.hm, that was way more than i paid, but i bought overseas at the time, so it might be different. I think selegiline and classic stims each have some + & - that the other doesn't, so they aren't totally interchangable.
Did you find it unhelpful when you took it?
-d/r
Posted by karl on December 19, 2008, at 15:15:07
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by desolationrower on December 19, 2008, at 13:39:59
i haven't taken amineptine. servier doesn't make it anymore and the only place i've seen it is on www.biopsychiatry.com where this pearce guy is pushing it pretty hard, at a premium markup since it's only made in small batches by a private laboratory.
from the way amineptine is described, it sounds like it feels like it's somewhere between wellbutrin and ritalin/cocaine on the "upper" spectrum. how did you find it?
i think selegiline confuses people because they don't understand which sensations are caused by which of its two actions. since it is both metabolized into meth AND inhibits mao-b, people have a hard time figuring out which of the two is doing what to them and at what times. i certainly have difficulty discerning and understanding the various feelings.
but if people are interested in seeing what pure mao-b inhibition feels like with a minimum of side effects, they should know that, like i said before, 2.5mg oral selegiline hydrochloride once per day is enough to inhibit 95% of the enzyme. again, that's according to this study.
and d/r, i want to take back taking back what i said earlier about selegeline's metabolism.
selegiline under the tongue [citrate or hydrochloride are the same thing, people ought not be fooled; the base doesn't matter.] is more invigorating because more selegiline is absorbed into the bloodstream than orally [wikipedia says 4.4% of the selegiline one swallows is absorbed into the bloodstream, i have no data on how much is absorbed sublingually, though it's certainly more], therefore more is converted into meth.
you're right in saying that sublingual selegiline doesn't undergo first-pass metabolism, but it is still readily metabolized by the liver whenever it gets there. and sublingually, it gets there quickly.
you're right, not through the portal vein, but through the "hepatic artery, a branch of a main heart artery called the aorta, which brings oxygenated blood from the heart to the liver. Sometimes up to a quarter of all the blood in the body is circulating through the liver."
source: http://www.cpmc.org/advanced/liver/patients/topics/liver-function.html
it seems like there's a lot of confusion out there about selegiline's action because of 1) its numerous properties [meth metabolites, mao-b inhibition, antioxidant] and 2) modes of delivery [tablet, liquid, patch] that entities of varying moral caliber have cooked up and it would be nice to have someone who really knows what they're talking about [unlike myself] clear up the matter on this board so that people who search for information on the once-simple selegiline molecule have something reliable to go on as they try to make themselves feel better so they don't have to listen to the [aptly named] GarbageMan. or me.
Posted by karl on December 19, 2008, at 17:40:03
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by karl on December 19, 2008, at 15:15:07
"when first-pass metabolism is circumvented, the maximum plasma concentration of selegiline is increased 60-fold and the balance of metabolites is altered significantly, halving the production of amphetamines..."
http://apple2.org.za/gswv/me/selegiline.structure.pdf
i'm going to stop pretending now that i have anything valuable to say about selegiline's metabolites.
but i'll stand by my point that people who take selegiline need to try to understand the different feelings they get from the two different actions of the drug, 1) metabolites and 2) mao-b inhibition. if it's the metabolites that are making them feel better, they should know that one can buy levo-methamphetamine at the drug store and that they may not need to order selegiline from overseas or pay $600/month for emsam patches. it's called levmetamfetamine now [to try to discourage abuse] and they put it in Vicks Inhalers, although according to wikipedia it's soaked in cotton and combined with menthol and camphor, so dosing is obviously tricky if not impossible. i don't know where one could obtain pure levmetamfetamine. if you know, kindly post a follow-up.
either way, if you feel like trying some mao-b inhibition on its own, you don't need much selegiline and you don't have to take it very often.
"MAO-B is irreversibly inhibited by 90% within 30-90 minutes, and remains so until it can be re-synthesized by the body -- a period of up to 40 days."
http://apple2.org.za/gswv/me/selegiline.structure.pdf
"...by 96 hours (four doses) the inhibition of platelet MAO-B activity is approximately 95% after a daily dose of 2.5 mg selegiline, whereas it takes only 48 hours (two doses) for doses of 5 mg and 7.5 mg to achieve this degree of inhibition."
in fact, i think i'll post this on its own for anyone searching for information on selegiline.
Posted by desolationrower on December 19, 2008, at 18:03:49
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by karl on December 19, 2008, at 15:15:07
Oh, i've not had amineptine, only selegiline. I was just wondering if you had it and disliked it, you seem not to. Just curious.
> i think selegiline confuses people because they don't understand which sensations are caused by which of its two actions. since it is both metabolized into meth AND inhibits mao-b, people have a hard time figuring out which of the two is doing what to them and at what times. i certainly have difficulty discerning and understanding the various feelings.
Keep in mind the mAMP that comes from selegiline is entirely the levo stereoisomer. So the effects will mainly be peripheral, rather like ephedrine, if you've ever used that.
> but if people are interested in seeing what pure mao-b inhibition feels like with a minimum of side effects, they should know that, like i said before, 2.5mg oral selegiline hydrochloride once per day is enough to inhibit 95% of the enzyme. again, that's according to this study.
>
> http://www.ncbi.nlm.nih.gov/pubmed/9853994?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumhm, that looks like a modeling study? in vivo human studies have shown more is required. i'm not sure there is a definative answer.
A dose-ranging study of selegiline in patients with Parkinson's disease: effect of platelet monoamine oxidase activity.
ABSTRACT
A dose-ranging study of selegiline was performed in patients with Parkinson's disease to determine the minimal dosage of the drug able to inhibit > or = 95% of platelet monoamine oxidase (MAO) activity. Different doses of selegiline (5 or 10 mg daily, 10 or 20 mg weekly) were studied in four groups of six patients with Parkinson's disease. Platelet MAO activity was measured before and after 1 month's treatment with selegiline. 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%). In contrast, platelet MAO-B inhibition was only 75.9% of the basal value after a dosage of 10 mg weekly. These results demonstrate that 20 mg weekly is the minimal dosage of selegiline able to induce a maximal and long-lasting inhibition of platelet MAO-B activity in patients with parkinsonism. Further clinical trials are needed to investigate the clinical efficacy of this dose.PMID: 9159721
> and d/r, i want to take back taking back what i said earlier about selegeline's metabolism.
>
> selegiline under the tongue [citrate or hydrochloride are the same thing, people ought not be fooled; the base doesn't matter.] is more invigorating because more selegiline is absorbed into the bloodstream than orally [wikipedia says 4.4% of the selegiline one swallows is absorbed into the bloodstream, i have no data on how much is absorbed sublingually, though it's certainly more], therefore more is converted into meth.
>
> you're right in saying that sublingual selegiline doesn't undergo first-pass metabolism, but it is still readily metabolized by the liver whenever it gets there. and sublingually, it gets there quickly.
>
> you're right, not through the portal vein, but through the "hepatic artery, a branch of a main heart artery called the aorta, which brings oxygenated blood from the heart to the liver. Sometimes up to a quarter of all the blood in the body is circulating through the liver."
>
> source: http://www.cpmc.org/advanced/liver/patients/topics/liver-function.htmlOk, look. Basically all of the selegiline hits the liver from oral ingestion. But it gets several cycles around the body from other forms of ingestion, and if it gets to the brain it inactivates MAOB. I'd encourage you to take a look at the testing data from the selegiline patch, theres a lot of stuff from there that backs this up.
Also, specific studies have been done on this question:
A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.
ABSTRACT
Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption "Zydis Selegiline" (1.25-10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as beta-phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96 mg) of a 10 mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute. Mean [SD] area-under-the curve (AUC(0- infinity)) values following Zydis Selegiline 10 mg (5.85 [7.31] ng.h/mL) were approximately five times higher than those following conventional selegiline tablets 10 mg (1.16 [1.05] ng.h/mL). In contrast, plasma concentrations of metabolites were significantly ( p<0.001) lower following Zydis Selegiline 10 mg than following conventional selegiline tablets 10 mg. Plasma concentrations of selegiline and its metabolites increased in a dose-dependent manner over the dose-range Zydis Selegiline 1.25-5 mg. Bioavailability was determined using AUC and peak plasma concentrations (C(max)). The C(max) of selegiline was similar following administration of Zydis Selegiline 1.25 mg (1.52 ng/mL) or conventional selegiline tablets 10 mg (1.14 mg/mL). The range of values for AUC(0- infinity) and C(max) following Zydis Selegiline 1.25 mg were entirely contained within the range following conventional selegiline tablets 10 mg, with a much higher variability of plasma selegiline concentrations occurring after conventional selegiline tablets than after Zydis Selegiline. As expected, peak plasma concentrations for DMS, AMT and MET were consistently lower after Zydis Selegiline 1.25 mg (1.19, 0.34, 0.93 ng/ml, respectively) than after conventional selegiline tablets 10 mg (18.37, 3.60, 12.92 ng/ml, respectively). A significant (r=0.0001) correlation between daily PEA excretion (a measure of brain MAO-B inhibition) and the log-transformed AUC((0-t)) for selegiline was demonstrated. Mean daily PEA excretion was similar following Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg (13.0 microg versus 17.6 microg). In contrast, there was no correlation between PEA excretion and selegiline metabolites, indicating that selegiline metabolites do not significantly inhibit MAO-B. Urinary excretion of 5-HIAA (used as a marker for MAO-A inhibition) was unrelated to plasma concentrations of selegiline or DMS following single or repeat dosing of Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg. However, comparison of treatment groups revealed a significantly lower excretion of 5-HIAA in the conventional selegiline tablets 10 mg group than in the Zydis Selegiline 1.25 mg group after repeated administration over 13 days. In summary, by reducing the opportunity for first-pass metabolism, the absorption of selegiline from Zydis Selegiline was more efficient and less variable than from conventional selegiline tablets. Compared with conventional selegiline tablets 10 mg, Zydis Selegiline 1.25 mg yielded similar plasma concentrations of selegiline and degree of MAO-B inhibition, but markedly reduced concentrations of the principal metabolites. Thus, the lower but equally MAO-B inhibitory dose of selegiline in Zydis Selegiline 1.25 mg, which is associated with lower concentrations of potentially harmful metabolites, could offer a safer and more predictable treatment in the management of patients with Parkinson's disease.PMID: 14628189 [PubMed - indexed for MEDLINE]
Hope that clears up some confusion.
-d/r
Posted by JadeKelly on December 19, 2008, at 18:56:54
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s » karl, posted by desolationrower on December 19, 2008, at 18:03:49
> Oh, i've not had amineptine, only selegiline. I was just wondering if you had it and disliked it, you seem not to. Just curious.
>
> > i think selegiline confuses people because they don't understand which sensations are caused by which of its two actions. since it is both metabolized into meth AND inhibits mao-b, people have a hard time figuring out which of the two is doing what to them and at what times. i certainly have difficulty discerning and understanding the various feelings.
>
> Keep in mind the mAMP that comes from selegiline is entirely the levo stereoisomer. So the effects will mainly be peripheral, rather like ephedrine, if you've ever used that.
>
> > but if people are interested in seeing what pure mao-b inhibition feels like with a minimum of side effects, they should know that, like i said before, 2.5mg oral selegiline hydrochloride once per day is enough to inhibit 95% of the enzyme. again, that's according to this study.
> >
> > http://www.ncbi.nlm.nih.gov/pubmed/9853994?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum
>
> hm, that looks like a modeling study? in vivo human studies have shown more is required. i'm not sure there is a definative answer.
>
> A dose-ranging study of selegiline in patients with Parkinson's disease: effect of platelet monoamine oxidase activity.
> ABSTRACT
> A dose-ranging study of selegiline was performed in patients with Parkinson's disease to determine the minimal dosage of the drug able to inhibit > or = 95% of platelet monoamine oxidase (MAO) activity. Different doses of selegiline (5 or 10 mg daily, 10 or 20 mg weekly) were studied in four groups of six patients with Parkinson's disease. Platelet MAO activity was measured before and after 1 month's treatment with selegiline. 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%). In contrast, platelet MAO-B inhibition was only 75.9% of the basal value after a dosage of 10 mg weekly. These results demonstrate that 20 mg weekly is the minimal dosage of selegiline able to induce a maximal and long-lasting inhibition of platelet MAO-B activity in patients with parkinsonism. Further clinical trials are needed to investigate the clinical efficacy of this dose.
>
> PMID: 9159721
>
> > and d/r, i want to take back taking back what i said earlier about selegeline's metabolism.
> >
> > selegiline under the tongue [citrate or hydrochloride are the same thing, people ought not be fooled; the base doesn't matter.] is more invigorating because more selegiline is absorbed into the bloodstream than orally [wikipedia says 4.4% of the selegiline one swallows is absorbed into the bloodstream, i have no data on how much is absorbed sublingually, though it's certainly more], therefore more is converted into meth.
> >
> > you're right in saying that sublingual selegiline doesn't undergo first-pass metabolism, but it is still readily metabolized by the liver whenever it gets there. and sublingually, it gets there quickly.
> >
> > you're right, not through the portal vein, but through the "hepatic artery, a branch of a main heart artery called the aorta, which brings oxygenated blood from the heart to the liver. Sometimes up to a quarter of all the blood in the body is circulating through the liver."
> >
> > source: http://www.cpmc.org/advanced/liver/patients/topics/liver-function.html
>
> Ok, look. Basically all of the selegiline hits the liver from oral ingestion. But it gets several cycles around the body from other forms of ingestion, and if it gets to the brain it inactivates MAOB. I'd encourage you to take a look at the testing data from the selegiline patch, theres a lot of stuff from there that backs this up.
>
> Also, specific studies have been done on this question:
>
> A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.
> ABSTRACT
> Seven randomised comparative studies were conducted in healthy volunteers to compare the pharmacokinetic and pharmacodynamic profiles of selegiline hydrochloride in a new formulation designed for buccal absorption "Zydis Selegiline" (1.25-10 mg) with conventional selegiline hydrochloride tablets "conventional selegiline tablets" (10 mg). A total of 156 healthy volunteers participated in these studies. Plasma concentrations of selegiline and its primary metabolites, N-desmethylselegiline (DMS), l-amphetamine (AMT), and l-methamphetamine (MET) were measured using Gas Chromatography Mass Spectrometry (GCMS) and gas liquid chromatography (GLC) assays. Inhibition of monoamine-oxidase type B (MAO-B) and monoamine oxidase type A (MAO-A) activity was determined by measurement of as beta-phenylethylamine (PEA) by GCMS and 5-hydroxyindoleacetic acid (5-HIAA) by High Performance Liquid Chromatography (HPLC) assays. Almost a third (2.96 mg) of a 10 mg selegiline dose in Zydis Selegiline was absorbed pre-gastrically (predominantly buccally) within 1 minute. Mean [SD] area-under-the curve (AUC(0- infinity)) values following Zydis Selegiline 10 mg (5.85 [7.31] ng.h/mL) were approximately five times higher than those following conventional selegiline tablets 10 mg (1.16 [1.05] ng.h/mL). In contrast, plasma concentrations of metabolites were significantly ( p<0.001) lower following Zydis Selegiline 10 mg than following conventional selegiline tablets 10 mg. Plasma concentrations of selegiline and its metabolites increased in a dose-dependent manner over the dose-range Zydis Selegiline 1.25-5 mg. Bioavailability was determined using AUC and peak plasma concentrations (C(max)). The C(max) of selegiline was similar following administration of Zydis Selegiline 1.25 mg (1.52 ng/mL) or conventional selegiline tablets 10 mg (1.14 mg/mL). The range of values for AUC(0- infinity) and C(max) following Zydis Selegiline 1.25 mg were entirely contained within the range following conventional selegiline tablets 10 mg, with a much higher variability of plasma selegiline concentrations occurring after conventional selegiline tablets than after Zydis Selegiline. As expected, peak plasma concentrations for DMS, AMT and MET were consistently lower after Zydis Selegiline 1.25 mg (1.19, 0.34, 0.93 ng/ml, respectively) than after conventional selegiline tablets 10 mg (18.37, 3.60, 12.92 ng/ml, respectively). A significant (r=0.0001) correlation between daily PEA excretion (a measure of brain MAO-B inhibition) and the log-transformed AUC((0-t)) for selegiline was demonstrated. Mean daily PEA excretion was similar following Zydis Selegiline 1.25 mg and conventional selegiline tablets 10 mg (13.0 microg versus 17.6 microg). In contrast, there was no correlation between PEA excretion and selegiline metabolites, indicating that selegiline metabolites do not significantly inhibit MAO-B. Urinary excretion of 5-HIAA (used as a marker for MAO-A inhibition) was unrelated to plasma concentrations of selegiline or DMS following single or repeat dosing of Zydis Selegiline 1.25 mg or conventional selegiline tablets 10 mg. However, comparison of treatment groups revealed a significantly lower excretion of 5-HIAA in the conventional selegiline tablets 10 mg group than in the Zydis Selegiline 1.25 mg group after repeated administration over 13 days. In summary, by reducing the opportunity for first-pass metabolism, the absorption of selegiline from Zydis Selegiline was more efficient and less variable than from conventional selegiline tablets. Compared with conventional selegiline tablets 10 mg, Zydis Selegiline 1.25 mg yielded similar plasma concentrations of selegiline and degree of MAO-B inhibition, but markedly reduced concentrations of the principal metabolites. Thus, the lower but equally MAO-B inhibitory dose of selegiline in Zydis Selegiline 1.25 mg, which is associated with lower concentrations of potentially harmful metabolites, could offer a safer and more predictable treatment in the management of patients with Parkinson's disease.
>
> PMID: 14628189 [PubMed - indexed for MEDLINE]
>
> Hope that clears up some confusion.
>
> -d/r
Hey d/r, sure cleared up any confusion I had.~Jade
Posted by Alucard on December 19, 2008, at 20:07:44
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s » desolationrower, posted by JadeKelly on December 19, 2008, at 18:56:54
There seems to be a lot of back and forth about how much of selegiline's activity is due to MAO-B inhibition and how much is due to its desmethylselegiline and LEVO-amphetamine and LEVO-methamphetamine metabolites (please quit calling it "meth". That's an ignorant slang name even for the substance to which it *actually* refers, DEXTRO-methamphetamine). I've given my two cents on Selegiline in plenty of earlier posts, but I did find something you all might find of value in regards to this question on the web earlier today.
Anybody here heard of a substance called Rasagiline (brand name Azilect)? I read about it a long time ago when it had just been developed by an Israeli pharmaceutical chemist and wasn't yet approved for public use in any Western nation. It has now been approved and can be found from a variety of online retailers (I'm not sure if prescriptions are available directly from US doctors yet but I know it's being prescribed in Europe). The reason I mention this is because Rasagiline selectively inhibits MAO-B (approximately 8-10 times more potently than Selegiline, meaning 1mg of Rasagiline shuts down about as much MAO-B as 10mg of Selegiline) BUT it metabolizes to aminoindan rather than levo-amphetamine & friends. So for those of you who aren't too keen on L-methylamphetamine, etc. floating around in your bloodstream on a daily basis but are still eager for some selective MAO-B inhibition this may be just the thing. It's new and definitely a lot pricier than Selegiline (even factoring in the 10x potency) but it doesn't have any questionable metabolites.
Personally, I'll stick with the liquid selegiline. I like drops better than pills and cheap better than expensive. When I stumble upon a fortune I may change my mind, but I've not discovered anything to convince me that minuscule doses of l-amphetamine or l-methylamphetamine are toxic, especially in the presence of the significant neuroprotective effects of selegeline itself. I am curious about the new MAO-B inhibitor though, so anybody with rasagiline experience please share your experience with us. And anybody with rasagiline AND selegiline experience PRETTY PLEASE post your experience. I'm sure others are curious as well...
Posted by Sigismund on December 19, 2008, at 22:32:07
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Alucard on December 19, 2008, at 20:07:44
I gave up using Cyprenil because it aggravated (rather than caused) my insomnia.
My experience was that deprenyl citrate had a different (and better) effect than the hydrochloride.
I'd try Azilect if it was cheaper.
Posted by ghimri on May 25, 2009, at 23:53:27
In reply to A few Cyprenil (liquid selegiline citrate) ?s, posted by Alucard on April 23, 2008, at 21:56:46
I've browsed through a few threads and the question alone. Sadly, none of you guys have any idea what you are talking about. Including the person who asked the question, when he stated Cyprenil is Selegiline Citrate. Cyprenil is Selegiline Hydrochloride guys. Cyto Pharma, a highly unethical Mexican company, purchases the Selegiline Hcl in bulk and dissolves it in what they refer to as "fresh water" on their package inserts.
Cyto Pharma is a fraud, attempting imitate Liquid Deprenyl Citrate (LDC), which was developed by a U.S. FDA registered, DEA Licensed pharmaceutical company. LDC is 99.99+% pure Selegiline freebase, mixed with Citragel. The Citragel stabilized the Selegiline so it could be conveniently administered, and it further carried the Selegiline through the blood brain barrier so that it would work. I don't know how anyone can talk about Selegiline, when no one has ever even seen it, only read about it. No one makes Selegiline at this point, and the only entity that posses it is not selling it.
Posted by Alucard on May 26, 2009, at 15:06:15
In reply to No one knows what they're talking about, posted by ghimri on May 25, 2009, at 23:53:27
Selegiline freebase isn't difficult to manufacture (the FDA-licensed company you referred to used CytoPharma's "unethical" Mexican manufacturing plant to make it for them), and neither is Citragel. If LDC is really so miraculous and the owners of the FDA-licensed company you mentioned are really the only people on the whole planet who know how to make it, why in God's name didn't they just go set up shop in another country after they got shut down here over 15 years ago? LDC has always been made by CytoPharma in Mexico, even when it was this American company selling it, the only difference is that now the Mexican company is selling it directly and the American company got shut down.
I think the FDA is a criminal organization too, I just don't see why the original makers of LDC gave up after one country shut them down. Does the rest of the world not deserve this miracle drug? Sounds to me like the original makers of LDC are either A. full of sh*t, B. paranoid schizophrenics, or C. themselves criminally negligent for not sharing the recipe after a decade and a half of not making it themselves. If they can't manufacture it themselves (for profit) because the FDA shut them down then they should at least tell the rest of the world how to do it so that humanity can still benefit.
Just doesn't make any damn sense to me.
> I've browsed through a few threads and the question alone. Sadly, none of you guys have any idea what you are talking about. Including the person who asked the question, when he stated Cyprenil is Selegiline Citrate. Cyprenil is Selegiline Hydrochloride guys. Cyto Pharma, a highly unethical Mexican company, purchases the Selegiline Hcl in bulk and dissolves it in what they refer to as "fresh water" on their package inserts.
>
> Cyto Pharma is a fraud, attempting imitate Liquid Deprenyl Citrate (LDC), which was developed by a U.S. FDA registered, DEA Licensed pharmaceutical company. LDC is 99.99+% pure Selegiline freebase, mixed with Citragel. The Citragel stabilized the Selegiline so it could be conveniently administered, and it further carried the Selegiline through the blood brain barrier so that it would work. I don't know how anyone can talk about Selegiline, when no one has ever even seen it, only read about it. No one makes Selegiline at this point, and the only entity that posses it is not selling it.
This is the end of the thread.
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