• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
* * * * * 1 votes

Selegiline (L-Deprenyl) - are there any dangers with taking this long term?

selegiline l-deprenyl deprenyl

  • Please log in to reply
12 replies to this topic

#1 Xenthide

  • Guest
  • 89 posts
  • 106
  • Location:England

Posted 27 March 2014 - 05:04 PM


I take 1.25mg Selegiline daily - at present I have only been taking it for a week or so, but I did go a couple of months last year before taking a break until recently.

I don't THINK I noticed any particular ill effects last year, but I am wondering - are there any dangers with taking this irreversible MAOI continuously?

I have no plans to increase my dosage, and I know that, supposedly, this chemical is selective for MAO-B at lower doses, but I spoke to a doctor last year who advised me strongly against continuing to take it, and said that no MAOI is completely selective, and I was still putting myself at risk for hypertensive crisis and, possibly, dangerous interactions with other substances.

However from my own research and subjective experience I haven't been able to find any information that indicates there is any real danger at the dose I am taking it at, or even, really, any dietary restrictions.


Can someone clear this up? Am I at risk in any way taking 1.25mg of selegiline daily long term?

Any information at all would be appreciated.

Edited by Xenthide, 27 March 2014 - 05:05 PM.


#2 Kevnzworld

  • Guest
  • 885 posts
  • 306
  • Location:Los Angeles

Posted 28 March 2014 - 04:24 PM

I was taking 5 mg every other day for about five months with no noticeable ill effect. I've reduced my intake to 2 mg every three days now, using the liquid vs the 5 mg pills.
I have been curious about the same concerns as the OP.

sponsored ad

  • Advert
Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

#3 Kevnzworld

  • Guest
  • 885 posts
  • 306
  • Location:Los Angeles

Posted 28 March 2014 - 11:19 PM

Coincidently I just read this blog post about Deprenyl today.
http://joshmitteldor...nti-aging-drug/

#4 tintinet

  • Guest
  • 1,972 posts
  • 503
  • Location:ME

Posted 31 March 2014 - 12:10 AM

I've been taking it for almost 20 years, and I'm still here, FWIW.

#5 chemicalambrosia

  • Guest
  • 393 posts
  • 59
  • Location:Minnesota, USA
  • NO

Posted 31 March 2014 - 01:04 AM

I've been taking it for almost 20 years, and I'm still here, FWIW.


What dosage and frequency have you taken it at? How would you rate your current motivation, drive, focus, etc that might be related to dopamine?

#6 LexLux

  • Guest
  • 265 posts
  • 88
  • Location:London, UK
  • NO

Posted 31 March 2014 - 01:59 AM

___________________________________________
The author has retracted this statement due to errors:

"Both selegiline and rasagiline supress mitochondrial apoptotic signaling and up-regulation anti-apoptotic bcl-2 and bcl-xL as well as prosurvival neurotrophic factors, including GDNF and BDNF. Further Rasagiline increases GDNF more markedly than BDNF and NGF (vice versa for selegiline)."


_____________
Correction:


"Rasagiline and (-)deprenyl (selegiline), irreversible type B monoamine oxidase (MAO-B) inhibitors, protect neuronal cells through gene induction of pro-survival Bcl-2 and neurotrophic factors in the cellular models of neurodegenerative disorders. In this paper, the role of MAO in the up-regulation of neuroprotective Bcl-2 gene by these inhibitors was studied using type A MAO (MAO-A) expressing wild SH-SY5Y cells and the transfection-enforced MAO-B overexpressed cells. Rasagiline and (-)deprenyl, and also befloxatone, a reversible MAO-A inhibitor, increased Bcl-2 mRNA and protein in SH-SY5Y cells. Silencing MAO-A expression with short interfering (si) RNA suppressed Bcl-2 induction by rasagiline, but not by (-)deprenyl. MAO-B overexpression inhibited Bcl-2 induction by rasagiline and befloxatone, but did not affect that by (-)deprenyl, suggesting the different mechanisms behind Bcl-2 gene induction by these MAO-B inhibitors. The novel role of MAO-A in Bcl-2 induction by rasagiline is discussed with regard to the molecular mechanism underlying neuroprotection by the MAO inhibitors."
(Inaba-Hasegawa K1, Akao Y, Maruyama W, Naoi M, Type A monoamine oxidase is associated with induction of neuroprotective Bcl-2 by rasagiline, an inhibitor of type B monoamine oxidase. J Neural Transm, 2012 Apr;119(4):405-14. doi: 10.1007/s00702-011-0730-6. Epub 2011 Nov 8.)



Bcl-2 induction is important because it inhibits apoptosis which may be desirable for parkinsons patients, but what about healthy people and our leading causes of death like cancer? "Aberrations in the BCL-2 family result in disordered homeostasis, a pathogenic event in diseases, including cancer."

"Bcl-2 and related cytoplasmic proteins are key regulators of apoptosis, the cell suicide program critical for development, tissue homeostasis, and protection against pathogens. Those most similar to Bcl-2 promote cell survival by inhibiting adapters needed for activation of the proteases (caspases) that dismantle the cell. More distant relatives instead promote apoptosis, apparently through mechanisms that include displacing the adapters from the pro-survival proteins. Thus, for many but not all apoptotic signals, the balance between these competing activities determines cell fate. Bcl-2 family members are essential for maintenance of major organ systems, and mutations affecting them are implicated in cancer."

For example, Bcl-2 also plays a functional role in lung cancer and nicotine induces cell (and cancer) survival in part via Bcl2 phosphorylation:

http://www.ncbi.nlm....pubmed/12421819

A functional role for nicotine in Bcl2 phosphorylation and suppression of apoptosis.
Mai H1, May WS, Gao F, Jin Z, Deng X.

Abstract
"Nicotine is not only a major component in tobacco but is also a survival agonist that inhibits apoptosis induced by diverse stimuli including chemotherapeutic drugs. However, the intracellular mechanism(s) involved in nicotine suppression of apoptosis is unclear. Bcl2 is a potent antiapoptotic protein and tumor promotor that is expressed in both small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) cells. It is possible that nicotine may regulate Bcl2 to stimulate cell survival. Here we report that nicotine can induce Bcl2 phosphorylation exclusively at the serine 70 site in association with prolonged survival of SCLC H82 cells expressing wild-type but not the phosphorylation-deficient S70A mutant Bcl2 after treatment with chemotherapeutic agents (i.e. cisplatin or VP-16). Nicotine induces activation of PKC alpha and the MAPKs ERK1 and ERK2, which are physiological Bcl2 kinases. Furthermore, ET-18-OCH3, a specific phospholipase C (PLC) inhibitor, blocks nicotine-stimulated Bcl2 phosphorylation and promotes apoptosis, suggesting that PLC may be involved in nicotine activation of Bcl2 kinases. Using a genetic approach, the gain-of-function S70E mutant, which mimics Ser(70) site phosphorylation in the flexible loop domain, potently enhances chemoresistance in SCLC cells. Thus, nicotine-induced cell survival results, at least in part, from a mechanism that involves Bcl2 phosphorylation. Therefore, novel therapeutic strategies for lung cancer in which Bcl2 is expressed may be used to abrogate the anti-apoptotic activity of Bcl2 by inhibiting multiple upstream nicotine-activated pathways."

One of the main reasons why curcumin is so appealing as a cancer fighting agent is it's ability to reduce Bcl-2 expression, leading to apoptosis in cancer cells: http://www.ncbi.nlm....pubmed/21595920

I am not an expert on this, or even involved in the medical field and my only intention is ask questions - A deceased nootropics enthusiast in fact died of brain cancer and he was taking deprenyl/selegiline daily.
More here http://www.groupsrv....bout168764.html

From his personal supplement regimen: http://www.antiaging...pplement-regime

"One of my favorite nootropics is liquid Deprenyl Citrate. I had used Jumex ® (Deprenyl HCL) intermittently over the years, but found that it didn't agree with me. It often made me irritable, anxious, "uptight" and even depressed at times. About 5 years ago Dr. Ward Dean convinced me to try the liquid Deprenyl, and much to my surprise I found it to be qualitatively different from Jumex. I find it to be an excellent mood elevator, psychoenergizer, and motivation-enhancer. It has improved my fine neuromuscular control, and seems to be a dopaminergic neuroprotector. I take 1-3 drops sublingually upon arising every morning. It may not be a coincidence that I've written more in the past few years than the previous decade."

Could it be detrimental for healthy people to take this chronically, given that it messes with Bcl-2 homeostasis? If apoptosis is suppressed via bcl-2 Induction consistently for years (presumably like in that guy) wouldn't cancer cells/tumors grow much more quickly? I just question the chronic use of these drugs as a life extension medication in healthy individuals.

Edited by cryonicsculture, 02 April 2014 - 07:29 PM.

  • like x 1

#7 LexLux

  • Guest
  • 265 posts
  • 88
  • Location:London, UK
  • NO

Posted 31 March 2014 - 03:05 AM

Im not saying deprenyl causes cancer, I'm just worried about the possibility of Bcl-2 over expression and its effects on cancer cell apoptosis in general.
  • Good Point x 1

#8 maximum411

  • Guest
  • 43 posts
  • 12
  • Location:Massachusetts

Posted 31 March 2014 - 07:29 AM

I believe deprenyl has been shown to extend lifespan in rats, so it at least benefits them in the long term. Of course, a rat is not a person.

#9 xEva

  • Guest
  • 1,594 posts
  • 24
  • Location:USA
  • NO

Posted 31 March 2014 - 08:27 PM

"Both selegiline and rasagiline supress mitochondrial apoptotic signaling and up-regulation anti-apoptotic bcl-2 and bcl-xL as well as prosurvival neurotrophic factors, including GDNF and BDNF. Further Rasagiline increases GDNF more markedly than BDNF and NGF (vice versa for selegiline)."


The quote is not in the link. And it looks wrong and contradictory. Was it supposed to be "both suppress and ..upreguate" instead of "both suppress signaling and upregulation"?

Edited by xEva, 31 March 2014 - 08:35 PM.


#10 LexLux

  • Guest
  • 265 posts
  • 88
  • Location:London, UK
  • NO

Posted 31 March 2014 - 10:28 PM

"Both selegiline and rasagiline supress mitochondrial apoptotic signaling and up-regulation anti-apoptotic bcl-2 and bcl-xL as well as prosurvival neurotrophic factors, including GDNF and BDNF. Further Rasagiline increases GDNF more markedly than BDNF and NGF (vice versa for selegiline)."


The quote is not in the link. And it looks wrong and contradictory. Was it supposed to be "both suppress and ..upreguate" instead of "both suppress signaling and upregulation"?


I'm sure I quoted that from the full text version, if you can access it you'll find it. It makes sense to me, supression of apoptotic signalling makes sense and up-regulation of Bcl-2 (anti-apoptotic)... so yeah.

Edited by LexLux, 31 March 2014 - 10:34 PM.


#11 LexLux

  • Guest
  • 265 posts
  • 88
  • Location:London, UK
  • NO

Posted 01 April 2014 - 03:10 AM

Eva you're right, I referenced in error , looking for the source. It should probably also read "as well as upregulating prosurvival..." Wish I knew where I tried to cite that from as I moved it here from my older thread: http://www.longecity...nf/page__st__30

My apologies that was sloppy, rest assured I'm not intentionally trying to mislead. The question I was trying to raise should not be affected by that mistake.

Perhaps a moderator could replace the quote with this one:

"Rasagiline and (-)deprenyl (selegiline), irreversible type B monoamine oxidase (MAO-B) inhibitors, protect neuronal cells through gene induction of pro-survival Bcl-2 and neurotrophic factors in the cellular models of neurodegenerative disorders. In this paper, the role of MAO in the up-regulation of neuroprotective Bcl-2 gene by these inhibitors was studied using type A MAO (MAO-A) expressing wild SH-SY5Y cells and the transfection-enforced MAO-B overexpressed cells. Rasagiline and (-)deprenyl, and also befloxatone, a reversible MAO-A inhibitor, increased Bcl-2 mRNA and protein in SH-SY5Y cells. Silencing MAO-A expression with short interfering (si) RNA suppressed Bcl-2 induction by rasagiline, but not by (-)deprenyl. MAO-B overexpression inhibited Bcl-2 induction by rasagiline and befloxatone, but did not affect that by (-)deprenyl, suggesting the different mechanisms behind Bcl-2 gene induction by these MAO-B inhibitors. The novel role of MAO-A in Bcl-2 induction by rasagiline is discussed with regard to the molecular mechanism underlying neuroprotection by the MAO inhibitors."
(Inaba-Hasegawa K1, Akao Y, Maruyama W, Naoi M, Type A monoamine oxidase is associated with induction of neuroprotective Bcl-2 by rasagiline, an inhibitor of type B monoamine oxidase. J Neural Transm, 2012 Apr;119(4):405-14. doi: 10.1007/s00702-011-0730-6. Epub 2011 Nov 8.)

Edited by LexLux, 01 April 2014 - 04:02 AM.


#12 tintinet

  • Guest
  • 1,972 posts
  • 503
  • Location:ME

Posted 02 April 2014 - 12:55 AM

I've been taking it for almost 20 years, and I'm still here, FWIW.


What dosage and frequency have you taken it at? How would you rate your current motivation, drive, focus, etc that might be related to dopamine?


When I first started taking it, eons ago,I took about 1 mg every 3rd day or so. Lately I've been taking 5 mg every third day or so. Never noticed any effects, but that's quite typical of my response (or lack thereof) to supplements and the like.
  • like x 1

sponsored ad

  • Advert
Click HERE to rent this advertising spot for SUPPLEMENTS (in thread) to support LongeCity (this will replace the google ad above).

#13 YOLF

  • Location:Delaware Delawhere, Delahere, Delathere!

Posted 02 April 2014 - 07:35 PM

Attention:
This post has been updated with a correction:
http://www.longecity...post__p__652994





Also tagged with one or more of these keywords: selegiline, l-deprenyl, deprenyl

1 user(s) are reading this topic

0 members, 1 guests, 0 anonymous users