![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 19 to 43 of 58. Go back in thread:
Posted by undopaminergic on April 28, 2008, at 10:12:46
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Amigan on April 28, 2008, at 7:31:56
> I'm not sure of this, but i feel that oral administration works better for me. It improves my mood much better than the sublingual administration which does very little for my mood.
>
> About the effects of Selegiline on NA that i keep reading about: Are there any evidences that Selegiline increases NA at MAO-B selective dose range and not just Dopamine and PEA?
>PEA and the amphetamines dose dependently release dopamine and noradrenaline. Amphetamines also release serotonin, but less potently and at higher doses than for the catecholamines.
Many people find amphetamines to be effective mood boosters, but tolerance and addiction are potential problems.
There is some evidence that selegiline is more noradrenergic than rasagiline, and that is probably due to the amphetamines, but there are very few studies comparing the two MAO-B inhibitors, and it may be interesting to note that they are all co-authored by Dr. Youdim, the "father" of rasagiline.
Posted by undopaminergic on April 28, 2008, at 20:11:50
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Alucard on April 27, 2008, at 1:49:08
> 1.25mg sublingual citrate = approx. 10mg oral hydrochloride?
>No, sublingual hydrochloride.
> Wow, no wonder such a difference in effects is reported between the two forms.
>
> Interesting thought: everybody who's done any amount of research on selegiline has come across the rat (and other mammal) studies where selegiline extended potential life span so dramatically. My question is this - what was the method of administration and exact formulation (citrate, hyrochloride, freebase in saline solution, or some other form entirely?) of the drug in those studies? If I had to guess I'd say that injection was the route of administration, and if that's the case then the more direct the route of administration the better (i.e. injection > patch > sublingual > oral). Hmmmmmm.
>Sublingual beats transdermal (the sublingual tissue is more permeable than regular skin).
Dr. Knoll used subcutaneous injections of 0.25 mg/kg L-deprenyl three times a week in his famous experiment where some of the selegiline-treated rats lived longer than the documented maximum life span of the rat strain in question. The abstract doesn't mention which form was used, but I presume it was the hydrochloride, because it's stable and readily soluble in water, whereas the freebase is reportedly volatile and poorly soluble.
It appears that the EMSAM patches use the freebase, which is a yellow to colourless oily liquid.
From what I've been able to discern, the so-called liquid selegiline citrate products are actually the freebase stabilised with citric acid and possibly other preservatives. In fact, I've been unable to find any proof of the existence of other forms of selegiline than the hydrochloride salt and freebase, although it would almost certainly be possible to produce some.
Some liquid selegiline products are reportedly mere aqueous solutions of the hydrochloride.
What is your liquid selegiline like? Is it an oily yellowish liquid, or does it seem more like water?
Posted by bulldog2 on April 29, 2008, at 8:40:10
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by undopaminergic on April 28, 2008, at 20:11:50
> > 1.25mg sublingual citrate = approx. 10mg oral hydrochloride?
> >
>
> No, sublingual hydrochloride.
>
> > Wow, no wonder such a difference in effects is reported between the two forms.
> >
> > Interesting thought: everybody who's done any amount of research on selegiline has come across the rat (and other mammal) studies where selegiline extended potential life span so dramatically. My question is this - what was the method of administration and exact formulation (citrate, hyrochloride, freebase in saline solution, or some other form entirely?) of the drug in those studies? If I had to guess I'd say that injection was the route of administration, and if that's the case then the more direct the route of administration the better (i.e. injection > patch > sublingual > oral). Hmmmmmm.
> >
>
> Sublingual beats transdermal (the sublingual tissue is more permeable than regular skin).
>
> Dr. Knoll used subcutaneous injections of 0.25 mg/kg L-deprenyl three times a week in his famous experiment where some of the selegiline-treated rats lived longer than the documented maximum life span of the rat strain in question. The abstract doesn't mention which form was used, but I presume it was the hydrochloride, because it's stable and readily soluble in water, whereas the freebase is reportedly volatile and poorly soluble.
>
> It appears that the EMSAM patches use the freebase, which is a yellow to colourless oily liquid.
>
> From what I've been able to discern, the so-called liquid selegiline citrate products are actually the freebase stabilised with citric acid and possibly other preservatives. In fact, I've been unable to find any proof of the existence of other forms of selegiline than the hydrochloride salt and freebase, although it would almost certainly be possible to produce some.
>
> Some liquid selegiline products are reportedly mere aqueous solutions of the hydrochloride.
>
> What is your liquid selegiline like? Is it an oily yellowish liquid, or does it seem more like water?I believe the 1.25 to 10 ratio is for zelapar the new sublingual tablet for pd. So we don't know if the liquids are absorbed that well.
On a more disconcerting note Discovery who made the first liquid depreynyl citrate which is now off the market claims that selepryl and ceprenyl are fakes and are just liquid selegiline hcl.
I wrote the company that makes these meds and asked them about that and have not heard from them yet.
Posted by alucard on April 29, 2008, at 16:54:32
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by bulldog2 on April 29, 2008, at 8:40:10
> What is your liquid selegiline like? Is it an oily yellowish liquid, or does it seem more like water?
undopaminergic - The Cyprenil I'm taking is a clear liquid the consistency of water that has a slightly bitter citric taste to it, so it's not the freebase.
>On a more disconcerting note: Discovery, who made the first liquid depreynyl citrate which is now off the market claims that selepryl and cyprenil are fakes and are just liquid selegiline hcl.
I wrote the company that makes these meds and asked them about that and have not heard from them yet.bulldog2 & undopaminergic & everybody - I too read Discovery's claim that Cyprenil and Selepryl were actually just liquid selegiline HCl intentionally mislabeled as the citrate, and I read that BEFORE I ordered the Cyprenil. Here's my thoughts on it:
First of all, as Discovery mentions on their website, they never actually made the liquid deprenyl citrate (LDC from now on) themselves, they contracted with a Mexican pharmaceutical company called Cyto-Pharma to make it for them. Apparently Discovery developed the PROCEDURE to make LDC, but then they licensed the use of that procedure to Cyto-Pharma so it could be made cheaply and then imported through Discovery. This is important because one of the so-called "fake" LDCs (Selepryl) is produced by a Mexican pharmaceutical company called...Cyto-Pharma. When Discovery's offices in Florida were raided and they were shut down in 1993, do you think all the chemists at Cyto-Pharma's lab in Mexico suddenly forgot the LDC manufacturing procedure? Definitely not, and on top of that chemists keep very detailed records of procedures. Furthermore, in the Mexican pharmaceutical market matters of licensing, patents, etc. are basically ignored, so Discovery getting shut down was actually just a free pass to Cyto-Pharma to sell their product directly to the American consumers of LDC under their own brand name (Selepryl instead of Discovery) with no competition (until Cyprenil came along of course).
Secondly, Discovery's claim that nobody else in the whole world has figured out how to make selegiline citrate is just plain ridiculous and insultingly unscientific, along with quite a few other claims on their website. I majored in organic chemistry in college and I can tell you this with certainty: practically any freebase that can be stabilized with hydrochloride can also be stabilized with citrate. Or, for that matter, with hydrogen cyanide (not that you'd want to use that particular one for ingestion), or any of a dozen other similar molecules. There are a few exceptions to this, BUT if one chemist can stabilize selegiline freebase with citrate, then so can anybody else with a year or two of organic chemistry training. It's just not that complex. So if Discovery can make selegiline citrate, then so can anybody else.
While we're on the subject of Discovery's claims about LDC, I may as well address this one too: Discovery claims that selegiline citrate is a "different chemical entity" than selegiline hydrochloride. This is technically TRUE, and it definitely matters when discussing subligually-absorbed selegiline. It doesn't matter if you simply swallow the LDC, because your stomach is filled with hydrochloric acid which will convert LDC to LD-Hydrochloride before it is absorbed. BUT if you absorb LDC through the mucus membrane under your tongue and in the rest of your mouth, you bypass that conversion to the hydrochloride form and allow the citrate form to go more or less directly into your bloodstream. Why is this important? Because sometimes stabilizer molecules (citrate, hydrochloride, hydrogen cyanide, etc.) have medically important effects themselves, and/or they interfere with the effect of the drug they are stabilizing. The stabilizer molecules can also aid or hinder absorption and use of the drug they are stabilizing. This can be seen most commonly in vitamins. Calcium citrate, for example, is better absorbed than tri-calcium phosphate, and is thus a better form to take if you must get your calcium from a pill. Both forms are "calcium", but they can technically be called "different chemical entities" because they absorb differently and are processed differently by your body. The same is true for selegiline citrate vs. selegiline hydrochloride, but ONLY when used sublingually or injected.
The Discovery scientists, while they were certainly pioneers of brilliant alternative therapies for many different ailments, appear to have become possessed by the persecuted-savior-complex. I have no doubt that they were intentionally screwed over and discredited by the FDA & Friends, but that doesn't mean that they are 100% correct about everything and beyond reproach. A good portion of their science and information is sound (including the majority of their "conspiracy" theories, in my opinion), but some of it is just a hysterical temper tantrum thrown by a toddler who's been treated unfairly. Like their claim that other people who are making LDC are liars and fakes. It sounds to me like they're just pissed that not only do they no longer have the LDC market cornered but they don't even have a little PIECE of that market any more. However, I have a hard time understanding why they don't just relocate to a foreign country if they really believe everything they write on their website. You'd think if you really believed you had cures for cancer and AIDS and old age, you might try a little harder to get them to the rest of the world? The FDA has no jurisdiction in Mexico or Canada or ANYWHERE except the U.S., and I hear Europe in particular is a lot more friendly to alternative medicine, but maybe I missed something...
Hope that was helpful and not too long or technical! For the record, I'll be ordering a few bottles of Selepryl to try after the Cyprenil runs out in 2 months and I'll post if I notice any subjective differences.
Posted by undopaminergic on April 30, 2008, at 13:53:58
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by alucard on April 29, 2008, at 16:54:32
> >On a more disconcerting note: Discovery, who made the first liquid depreynyl citrate which is now off the market claims that selepryl and cyprenil are fakes and are just liquid selegiline hcl.
> I wrote the company that makes these meds and asked them about that and have not heard from them yet.
>
> bulldog2 & undopaminergic & everybody - I too read Discovery's claim that Cyprenil and Selepryl were actually just liquid selegiline HCl intentionally mislabeled as the citrate, and I read that BEFORE I ordered the Cyprenil. Here's my thoughts on it:
>
> First of all, as Discovery mentions on their website, they never actually made the liquid deprenyl citrate (LDC from now on) themselves, they contracted with a Mexican pharmaceutical company called Cyto-Pharma to make it for them. Apparently Discovery developed the PROCEDURE to make LDC, but then they licensed the use of that procedure to Cyto-Pharma so it could be made cheaply and then imported through Discovery.
>I don't think Cyto-Pharma was given the procedure for making selegiline, only for formulating the so-called "Liquid Deprenyl Citrate" (trade mark). At least according to:
http://www.imminst.org/forum/index.php?showtopic=303&st=0&p=2931&#entry2931Quotation of the relevant passage:
"The procedure to only formulate Liquid Deprenyl Citrate was given to Cyto Pharma, but not the procedure for manufacturing deprenyl. The procedure to manufacture deprenyl free base was given to another company in Mexico. The deprenyl free base was then provided to Cyto Pharma to formulate into Liquid Deprenyl Citrate."> > What is your liquid selegiline like? Is it an oily yellowish liquid, or does it seem more like water?
>
> undopaminergic - The Cyprenil I'm taking is a clear liquid the consistency of water that has a slightly bitter citric taste to it, so it's not the freebase.
>So you believe it's an aqueous solution of the citrate salt of selegiline?
Without further data, I would assume it's a solution of the hydrochloride, because no-one has (to my knowledge) ever reported the preparation of a citrate salt of selegiline. Therefore, the characteristics (melting point, solubility, stability, etc.) of such a compound are unknown.
Theoretically, the molecular weight of selegiline citrate would be 379.40. Therefore 2.03 mg of selegiline citrate would correspond to 1 mg of the freebase, or 1.19 mg of the hydrochloride. You would need to take this into account when determining the dosage.
Posted by bulldog2 on April 30, 2008, at 16:00:07
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by undopaminergic on April 30, 2008, at 13:53:58
So selepryl or cyprenil are really selegiline hcl?
Posted by undopaminergic on April 30, 2008, at 16:37:22
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by bulldog2 on April 30, 2008, at 16:00:07
I think they very well might be. However, I'm just speculating. The truth would be easy to find out in theory, but who's willing to spend the money and effort on sending a sample of these products to a laboratory for analysis?
Posted by bulldog2 on April 30, 2008, at 17:16:36
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by undopaminergic on April 30, 2008, at 16:37:22
> I think they very well might be. However, I'm just speculating. The truth would be easy to find out in theory, but who's willing to spend the money and effort on sending a sample of these products to a laboratory for analysis?
I wrote the company that produces these products about my concerns and they have yet to respond.
Posted by alucard on May 1, 2008, at 2:11:12
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by bulldog2 on April 30, 2008, at 17:16:36
I agree with you guys that Cyprenil and Selepryl could quite easily be selegiline HCl, especially given the "flexibility" of Mexican pharmaceutical purity and labeling standards. However, as a chemist I know that it just isn't that difficult to make the citrate form if you've already got a lab equipped to make the hydrochloride form. So why lie about it? There's always the possibility that two separate companies ARE just making the hydrochloride salt and lying about it, but I fail to see the motive when it's so easy to make the real thing and stay honest...
Another related point: the main pharmaceutical chemist who testified FOR Discovery in their lawsuits wrote an affidavit stating that his professional opinion was that the superiority of Discovery's product lay in their purification procedures, NOT in the specific ion (citrate vs. hydrochloride) that they stabilized the selegiline with. So who knows? I think at this point it's pretty much subjective opinion about efficacy, regardless of whether it's citrate or hydrochloride...
Which still doesn't answer the most curious question of all: if Discovery REALLY discovered all these great cures and they're completely prevented from making a profit off of them by the FDA, why the hell don't they just distribute the manufacturing instructions as widely as possible? Sketchy stuff...
Posted by undopaminergic on May 2, 2008, at 12:26:23
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by alucard on May 1, 2008, at 2:11:12
> I agree with you guys that Cyprenil and Selepryl could quite easily be selegiline HCl, especially given the "flexibility" of Mexican pharmaceutical purity and labeling standards. However, as a chemist I know that it just isn't that difficult to make the citrate form if you've already got a lab equipped to make the hydrochloride form. So why lie about it?
>Perhaps they don't have a lab equipped to synthesise selegiline, or perhaps they don't have the skills? Perhaps they just buy it from bulk chemical suppliers? In that case they will find the hydrochloride to be the most readily available, whereas the freebase is quire rare, and the citrate absolutely unheard of.
Also, since the properties of the citrate salt of selegiline are unknown, we don't know whether it's water soluble or otherwise suitable for bottling and distribution.
Since you're a chemist, have you considered trying to make your own selegiline - citrate or otherwise? Aren't you at least tempted to evaporate the water from some of your Cyprenil and determine the melting point of the residue? And perhaps hydrolyse it with a base and see whether you get the oily free base of selegiline? Maybe you even have some contacts within the industry who could help you with HPLC, GCMS, or other advanced methods of analysis?
Posted by bulldog2 on May 2, 2008, at 14:32:42
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by undopaminergic on May 2, 2008, at 12:26:23
Dedi also made some remark about selepryl and cyprenyl not crossing the blood brain barrier. Not sure how they came to that conclusion.
Posted by undopaminergic on May 2, 2008, at 17:49:56
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by bulldog2 on May 2, 2008, at 14:32:42
> Dedi also made some remark about selepryl and cyprenyl not crossing the blood brain barrier. Not sure how they came to that conclusion.
>Some of their writings are just ridiculous and nonsensical. There is overwhelming proof that selegiline - whether in its free base or hydrochloride form - is centrally active.
Posted by Amigan on May 3, 2008, at 0:07:03
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by alucard on May 1, 2008, at 2:11:12
Why do you care so much if it's citrate or HCL? Does it even matter?
Posted by Alucard on May 3, 2008, at 2:56:34
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Amigan on May 3, 2008, at 0:07:03
>Why do you care so much if it's citrate or HCL? Does it even matter?
It might, and it might not. It all depends on what form was used in the animal experiments that have yielded such positive results. The original creators of the citrate form (DEDI) have been rather intense about citrate being the only truly effective form, but quite a few claims they make are pretty seriously sketchy (e.g. nobody else in the WHOLE WORLD knows how to manufacture the citrate form), so I take them with 20 or 30 grains of salt.
>Perhaps they (Cyto-Pharma) don't have a lab equipped to synthesise selegiline, or perhaps they don't have the skills?
Selegiline freebase is extremely easy to make with cheap, readily available chemicals. If you were really determined to do it you could make it at home with chemicals acquired at a reasonable cost from your local hardware store and Wal-Mart, or dirt cheap from the internet. So any laboratory of any size, ESPECIALLY a pharmaceutical lab, would definitely be equipped and skilled enough to make it. Making it at home is a BAD IDEA, however, because your product would be nowhere near 99.99% pure and those little impurities can have a HUGELY negative effect. Pharmaceutical labs in particular are very careful to purify their products extensively for this very reason (one fatal mistake and chances are you're going out of business from the bad publicity and ensuing lawsuits, and possibly facing prison time).
>Since you're a chemist, have you considered trying to make your own selegiline - citrate or otherwise? Aren't you at least tempted to evaporate the water from some of your Cyprenil and determine the melting point of the residue? And perhaps hydrolyse it with a base and see whether you get the oily free base of selegiline? Maybe you even have some contacts within the industry who could help you with HPLC, GCMS, or other advanced methods of analysis?
VERY tempted, and not just selegiline but a whole host of other interesting compounds I've come across throughout the years. BUT I'm kinda wandering around the world with nothing more than I can carry in a backpack at the moment, and will be for the indefinite future. This year I'm in Hawai'i, hence my ability to check this forum every few days, but it'll be awhile before I settle down enough (if I ever do) to put a functional lab together and play around with the molecular world first-hand again. As for analysis of the Cyprenil, I'm honestly very surprised that nobody has published anything along those lines on the internet yet (at least that I've been able to find), especially given all the hullaballoo about citrate vs. hydrochloride. Of course DEDI claims that Cyprenil and Selepryl are both fake, but where is the proof? An independent analysis or two is easy enough to get done as a favor if you're a pharmaceutical distributor (even an EX-pharmaceutical distributor), which they are, and the report would be easy enough to upload if you've got your own website, which they do. Yet as with many of their space cadet claims, they don't bother with irrelevant fluff like...proof. That, to me, is strong evidence that they're full of sh*t.
As for me personally, I'm enjoying the effects of the selegiline I've got, whatever form it may be (I feel like I'm getting my A-game back more and more every day, and it hasn't even been 2 weeks). I ordered some capsules of Mucuna pruriens bean extract to synergize with it and cost-effectively augment its effects (since the bean extract is much cheaper than the selegiline). I've heard good things about the combo, the Mucuna pruriens has a hefty amount of dopamine precursors in it, quite a few neuroprotective compounds, etc. so it sounds like selegiline's perfect other half to me.
Mahalo kids =)
Posted by undopaminergic on May 3, 2008, at 11:20:59
In reply to Re: A few Cyprenil (liquid selegiline citrate) ?s, posted by Alucard on May 3, 2008, at 2:56:34
>
> As for me personally, I'm enjoying the effects of the selegiline I've got, whatever form it may be (I feel like I'm getting my A-game back more and more every day, and it hasn't even been 2 weeks).
>Cool. I noticed the strongest effect on the first day, but no improvement over time.
> I ordered some capsules of Mucuna pruriens bean extract to synergize with it and cost-effectively augment its effects (since the bean extract is much cheaper than the selegiline). I've heard good things about the combo, the Mucuna pruriens has a hefty amount of dopamine precursors in it, quite a few neuroprotective compounds, etc. so it sounds like selegiline's perfect other half to me.
>I tried that combination too, but it worked very poorly, so I tried L-dopa+benserazide instead of the herb, but that wasn't really any better.
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!
Go forward in thread:
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.