57 replies to this topic

[zoolander]

I think it's time to spike my drink again with deprenyl

J Neural Transm Suppl. 2006;(71):143-56.

    Deprenyl: from chemical synthesis to neuroprotection.

        * Magyar K,
        * Palfi M,
        * Jenei V,
        * Szoko E.

    Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary. kalman.magyar@net.sote.hu

    During the last decades (-)-deprenyl has become the golden standard of MAO-B inhibitors. It possesses dopamine potentiating and antioxidant properties; however, its effects cannot be explained solely by the enzyme inhibitory action. (-)-Deprenyl prevents the toxicity of certain selective neurotoxins and recently it was demonstrated to increase cell-cell adhesion as well. The complexity of its pharmacological effects reflects the action of both the parent compound and the active metabolites. (-)-Deprenyl and related propargylamines (DRPs) show neuroprotective features in a variety of in vitro and in vivo models that is dependent on the propargyl moiety. The main presumptive targets to date include glyceraldehyde-3-phosphate dehydrogenase, poly(ADP-ribose) polymerase, some kinase cascades, as well as pro- and antiapoptotic proteins, beside the inhibition of MAO-B. The antiapoptotic activity of DRPs converges upon the maintenance of mitochondrial integrity, due to the initiation of a complex transcriptional program, the details of which are yet to be elucidated.

    PMID: 17447425 [PubMed - indexed for MEDLINE]

[luv2increase]

How did you react with taking deprenyl Zoo? Why did you discontinue?

[zoolander]

It's very uplifting for me. An amazing sense of wellness. Even though life has always been a wonderful thing for me, deprenyl really makes me stop and cherish the moment. You know......when you stop and go "WOW, how beautiful is life".

Unfortunately for my partner, who does not deal well with too much catecholamine, this is not the case.

[scottl]

Good timing I was just thinking to add this back.

What dose are you taking that you notice effects?

[zoolander]

Scottl, how the hell are you matey.

well I use to use roughly 1mg 3 x per week (Mon, Wed, Fri) and on occasions would take 2.5 or 5mg in one dose.

The low dose transdernal patch system looks promising

[shifter]

Where do you guys get access to it? I just when to a chemist and they said I needed a doctors script for it. Is it something a doctor may have issues giving to healthy looking fit 25 year olds?

[shifter]

Deprenyl has also protected human nerve cells from peroxynitrite and nitric oxide toxicity.  Peroxynitrite is formed naturally in the brain when nitric oxide reacts with superoxide radical.  Peroxynitrite causes �apoptosis�, a programmed �suicide� cell death that can be triggered in neurons by various agents.  deprenyl was found to inhibit peroxynitrite-caused apoptosis, even after the deprenyl was washed from deprenyl pre-treated cells.  (3)

Methyl-salsolinol is another MAO-B produced endogenous neurotoxin.  Salsolinol is a tetra-hydroisoquinoline produced from the interaction of dopamine and acetaldehyde, the first-stage breakdown product of alcohol. 

Once formed, salsolinol can then be further modified by MAO-B to generate methyl-salsolinol. deprenyl's  MAO-B inhibiting activity can prevent the DNA damage caused by this toxin. (3, 4)

By inhibiting MAO-B, deprenyl reduces the toxic load on the brain that is routinely produced through the normal operation of MAO-B. MAO-B digests not just dopamine and PEA, but also tryptamine, tyramine and various other secondary and tertiary amines. (15)

As noted earlier, PEA is the substance MAO-B is most efficient at digesting, so that the half-life of PEA is estimated at only 0.4 minutes. (21) 

This continuous high level breakdown of PEA (and other amines) produces aldehydes, hydrogen peroxide and ammonia as automatic MAO-B reaction products, and they are all toxins. (4)  Thus by reducing age-elevated MAO-B activity, deprenyl reduces the toxin burden on dopamine/noradrenalin neurons (where PEA is primarily produced).

link: http://www.deprenyl.net/

So half life of PEA is only 0.4 minutes? I guess considering the breakdown of PEA produces toxins, it might be better to not take PEA on its own? What about cocoa?

[shifter]

Cool, I got some (called selegiline hydrochloride and brand eldepryl) and they come in 5mg doses. It says to take it every day. However I split a few in half and will take those first. I see some of you take it every other day.... Is this something that builds up in the system if taken every day?

Have to stop the sam-e and 5htp now though. Is Melatonin still okay to take while on this?

If this has given rats an extra 20% maximum lifespan, why is it not as popular as the resveratrol?

I suppose I can put all my blueberry juice and cocoa to better use seeing as the goodies wont break down so quick.

Is the organic raw cocoa a good source of PEA? (eg will a table spoon of nibs or powder give me a good dose like I bought PEA on its own). I think I might not be allowed to import PEA to Oz :( (silly me tried to find this out AFTER an order had been made and shipped out!!)

[sentinel]

Scottl, you're alive! Always good to have a GP/MD input.

Zoolander, can I ask what brand/form you use(d). I have tried Deprenyl before (Juprenil selegilin) at doses varying from 2.5 mg every 2 - 3 days thru to 5mg per day c 5 days per week, but generally found to mood and "drive" aspects unnoticable and, at higher doses, mental fog and general fogginess which is, at best, ironic!

Do you think it's (mood/drive) effectiveness could depend on whether someone has naturally low (or high) Dopamine levels..?

sentinel

[betty]

Sentinel, have you tried sublingual?

[sentinel]

Sort of. As I had pills I had to crush them, wait for it to dissolve and pull faces as it doesn't taste great.

I haven't seen a lot of consensus for it being more effective (better absorption perhaps but not nec. a better end result ) either but feel free to correct me as it has been a year since I stopped.

sentinel

[sentinel]

Bump. Any input on sources/brands and forms (ie liquid vs tablet).

Thanks

Sentinel.

[Karomesis]

Any input on sources/brands and forms (ie liquid vs tablet).

I order mine from here http://www.antiaging...g/deprenyl.html the only downside being it takes about 3 weeks for shipping.

the liquid tastes pretty bad, dilution in something strong is the best method of ingestion.


as for bioavailability I found this

http://www.ncbi.nlm....Pubmed_RVDocSum

indicating buccal(between the cheek and gum) administration is superior to regular tablets.

[sentinel]

thanks karomesis, how did it work out for you? Were you doing 1mg per day or going for it like the M&M Forum boys 10mg+ per day [huh]

[Karomesis]

Were you doing 1mg per day or going for it like the M&M Forum boys 10mg+ per day

I was doing about 3mg/day and it performed as expected and then some. Be VERY careful when dosing with this stuff Sentinel, if you notice any irritable effects I'd take a break and wait until it wears off a little before starting up again.

My sex drive is already through the roof so it didn't do much for me on that end. But it DID make me more prone to dangerous bouts of anger akin to a "roid rage" type of effect, along with causing me to have more pep in my step and become even more ambitious/driven than I was already. It seemed to take certain behavoiral traits and intensify them even more.

If I took 10 mg/day I'd probably start pillaging and plundering local villages [:o]

[FunkOdyssey]

That study suggests 1.25mg of sublingual/buccal deprenyl produces the same plasma concentration of selegiline as 10mg of an oral tablet, with much lower concentrations of [toxic] metabolites, and less MAO-A inhibition. If this is true, there is really no comparison between oral / liquid deprenyl at the same dose (results should be radically different).

As I had pills I had to crush them, wait for it to dissolve and pull faces as it doesn't taste great.

In light of the new information, I'm going to have to try this myself. [sick]

Edited by FunkOdyssey, 13 June 2007 - 07:35 PM.

[FunkOdyssey]

Here's the study with the important points highlighted:

J Neural Transm. 2003 Nov;110(11):1241-55.

    A new formulation of selegiline: improved bioavailability and selectivity for MAO-B inhibition.
    Clarke A, Brewer F, Johnson ES, Mallard N, Hartig F, Taylor S, Corn TH.

    Scherer DDS, Swindon, United Kingdom. aclarke@cephalon.com

    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]

[kottke]

I myself have been thinking about getting back on a low dose of deprenyl, probably 1mg daily. Awhile back i played around with 2.5-5.0mgs with variable results so we'll see how it goes. That is 1mg of the regular liquid deprenyl formulation not the Zydis

[sentinel]

If I took 10 mg/day I'd probably start pillaging and plundering local villages

Just the local villages then [pirate] [lol]

FunkO

That study suggests 1.25mg of sublingual/buccal deprenyl produces the same plasma concentration of selegiline as 10mg of an oral tablet

Good informtation. Time to try the liquid I think, at least it probably won't hang around in my mouth as long as crushed pills.

I'll probably give one of karomesis' recommendations a try (althought 3 weeks...!) and report back to any interested parties. To horse!

Sentinel.

[ageless]

Deprenyl has interested me for years, but I haven't yet tried it... interesting that recently a company came out with a patch version with use of an antidepressant. I wouldn't mind seeing how it might benefit me and increased motivation would not be a bad idea.

[sentinel]

I was drawn by the "motivation" thing but, as with other noops, this way only work for people who have a particular short falling (in dopamine, serotonin etc) which is being "normalised" rather than giving someone with regular baseline levels a particular edge.

I will give the liquid a shot and if that does nothing (good) then it will just join the long "Doesn't work or quietly keeping me alive longer" list along with rhodiola etc.

Unfortunately AAS (as kindly recommended by Karomesis) don't ship to UK so I'll track another source.

Sentinel

[kottke]

Does anyone know of a direct contradiction with Deprenyl and St Johns Wort? I know there is a theoretical issue there but ive not seen any direct interaction throughout the web. I take 900mgs daily of research grade SJW containing 3% hypericin and 4% hyperforin. Thanks

[jackj]

Hello, after searching due to delays in shipping my deprenyl and pirac i came across this

http://herbalpowers....r120ca10o1.html - Mucuna Pruriens,

from what i've seen its only for short term use and perhaps nurotoxic? is it a viable alternative to deprenyl?

[medievil]

Does anyone know of a direct contradiction with Deprenyl and St Johns Wort? I know there is a theoretical issue there but ive not seen any direct interaction throughout the web. I take 900mgs daily of research grade SJW containing  3% hypericin and 4% hyperforin. Thanks

not if you take a low dose of dep

[kottke]

medievil: yea i guess its one of those things that i have to use strong judgement upon with the given information out on the net.Its risky but i do think 1mg a day would be safe seeing as some people take 12mgs EMSAM infusions daily on top of SSRIs.

unlucid: Mucuna Pruiriens doesn't have the numerous health extending & neuroprotective benefits that deprenyl may possess. It also may make you crazy

[evilrabbitry]

"Mucuna Pruiriens doesn't have the numerous health extending & neuroprotective benefits that deprenyl may possess. It also may make you crazy"

Can you source this or some other precautionary information for velvet bean?

[kottke]

Ok thats a bit subjective. I should have said "velvet bean would probably make kottke crazy" or something along those lines. Mucuna Pruiriens is powerful from what ive read and stimulating dopamine that much may make certain susceptible individuals "crazy". This is known with all dopamine agonists. But you know if that stuff works for you go for it; just dont expect it to have the same beneficial properties as deprenyl. They are both very different substances

[evilrabbitry]

fair enough.....i wasnt calling you out or anything, i was more aroused by my own use of mucuna in the past for its effects on body composition....for which, i have found to be surprisingly effective.

[graatch]

L-DOPA has a very established profile of long-term side effects. Be very careful.