Aicar

[bbmg33]

Has anyone out there heard of this new drug or know anything about it? There isn't much info on the web about it. I saw an article in the LA Times about it and wanted some more info...Any assistance would be appreciated!

-Kristina

 

[JohnnieFreeze]

Ive read that same article....."Researchers experiment with a chemical compound that they say can produce the benefits of aerobic activity without the work."

Link to the article...sounds like at least a piece of that "magic pill"

http://www.latimes.com/features/health/medicine/la-sci-couchpill1-2008aug01,0,4249687.story

 

[WilteredFire]

L-Carnitine Supplementation: A New Paradigm for its Role in Exercise

William J. Kraemer , Jeff S. Volek, Barry A. Spiering, and Jakob L. Vingren

Human Performance Laboratory, Department of Kinesiology, Department of Physiology
and Neurobiology, University of Connecticut, Storrs, CT USA 06269

Received October 20, 2004; accepted November 24, 2004
Published online June 10, 2005 Springer-Verlag 2005

Summary. Early research investigating the effects of L-carnitine supplementation has examined its role in substrate metabolism and in acute exercise performance. These studies have yielded equivocal findings, partially due to difficulties in increasing muscle carnitine concentrations. However, recent studies have proposed that L-carnitine may play a different role in exercise physiology, and preliminary results have been encouraging. Current investigations have theorized that L-carnitine supplementation facilitates exercise recovery. Proposed mechanism is as follows: 1) increased serum carnitine concen-tration enhances capillary endothelial function; 2) increased blood flow and reduced hypoxia mitigate the cascade of ensuing, destructive chemical events following exercise; 3) thus allowing reduced structural damage of skeletal muscle mediated by more intact receptors in muscle needed for improved protein signaling. This paradigm explains decreased markers of purine catabolism, free radical forma-tion, and muscle tissue disruption after resistance exercise and the increased repair of muscle proteins following long-term L-carnitine supplementation.

======

Try pull up some info and research on the new version of Alcar called PLCAR, this is where the Carnitine limelight is focused on right now i reckon, Alcar basically is used for more focus, energy in the gym, to enhance mood (yes you can generally feel a more happy feeling after a small dose of Alcar, i can feel it after 150-200mg's with water), the other area of interest in this substance seems to be fatloss, and its apparant abilitys in getting your body to use fat as fuel for enegy, and if i remember correctly, the PLCAR and Alcar seems to have the ability to refresh/create AR's, good for people who want to take steroids/ph's and get as good gains as they do with their first cycle.

Please somebody correct me if im wrong, this is just what I know about Alcar. People who have been injecting Alcar have been reporting promising results for fatloss. PLCAR looks more promising though

 

[sportsterdann]

Aicar not Alcar..

 

[mtlbob]

The article about AICAR

Has anyone out there heard of this new drug or know anything about it? There isn't much info on the web about it. I saw an article in the LA Times about it and wanted some more info...Any assistance would be appreciated!

-Kristina

This is the original article about AICAR. Can't wait to get it!!!

CELL
Volume 134, Issue 3, 8 August 2008, Pages 405-415
doi:10.1016/j.cell.2008.06.051

AMPK and PPARδ Agonists Are Exercise Mimetics

Vihang A. Narkar1, Michael Downes1, Ruth T. Yu1, Emi Embler1, Yong-Xu Wang4, Ester Banayo3, Maria M. Mihaylova2, Michael C. Nelson1, Yuhua Zou1, Henry Juguilon1, Heonjoong Kang5, Reuben J. Shaw2 and Ronald M. Evans1, 3, ,

1Gene Expression Laboratory, Salk Institute, La Jolla, CA 92037, USA 2Molecular and Cell Biology Laboratory, Salk Institute, La Jolla, CA 92037, USA 3Howard Hughes Medical Institute, La Jolla, CA 92037, USA 4University of Massachusetts Medical School, Worcester, MA 01605, USA 5Marine Biotechnology Laboratory, School of Earth and Environmental Sciences, Seoul National University, Seoul 151-747, South Korea

Received 30 May 2007; revised 23 April 2008; accepted 20 June 2008. Published online: July 31, 2008. Available online 31 July 2008.

Can Exercise Mimetics Substitute for Exercise?

Cell Metabolism, Volume 8, Issue 2, 6 August 2008, Pages 96-98
Erik A. Richter, Bente Kiens, Jørgen F.P. Wojtaszewski
PDF (202 K)

Summary

The benefits of endurance exercise on general health make it desirable to identify orally active agents that would mimic or potentiate the effects of exercise to treat metabolic diseases. Although certain natural compounds, such as reseveratrol, have endurance-enhancing activities, their exact metabolic targets remain elusive. We therefore tested the effect of pathway-specific drugs on endurance capacities of mice in a treadmill running test.

We found that PPARβ/δ agonist and exercise training synergistically increase oxidative myofibers and running endurance in adult mice. Because training activates AMPK and PGC1α, we then tested whether the orally active AMPK agonist AICAR might be sufficient to overcome the exercise requirement. Unexpectedly, even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. These results demonstrate that AMPK-PPARδ pathway can be targeted by orally active drugs to enhance training adaptation or even to increase endurance without exercise.

Author Keywords: SIGNALING

 

[larrypearson1]

I'm still trying to get AICAR in pill form or as peptide from reliable supplier. Anyone have any info on where to purchase GW1516?

send private message if you know about potential AICAR SUPPLEMENT or other sources.

 

[propho]

AICAR sounds interesting but DAMN! it's hella expensive at the moment..

 

[tcshZion]

Can anyone tell me where to buy this? Also, what, in theory, would be the effective human dose?


:thanks:
--tcshZion

 

[mixmike007]

have you got any protocol for aicar cycle ? SC , IM ? Every day ? every one day ? ...
thanks

 

[lonewolf0420]

" The drug appeared to change the physical composition of muscle, essentially transforming the tissue from sugar-burning fast-twitch fibers to fat-burning slow-twitch ones, "

Isn't that the opposite of what a bodybuilder wants.

 

[BigNemo]

forget about this stuff 4 quite some time it would cost thousands a month for an average sized person just spend the money on gym membership and of course tren igf-1 and throw in a lil methyl drostenalone way cheaper and prob as effective if not better

 

[Fried Cheese]

Does AICAR destroy muscle?

Does AMPK Play a Role in Sarcopenia?

Gradual basal skeletal muscle atrophy with age (sarcopenia) is perhaps even more clinically significant than diminished overload-induced growth. The fact that AMPK activity displays a five-fold increase with age in resting fast-twitch, but not slow-twitch, muscle (Figure 1)[25] led us to speculate that AMPK may partly underlie basal fast-twitch specific atrophy, an effect not testable by acute AMPK activation studies. Thus, we continuously activated AMPK in the resting muscles of young and old rats for 7 d (AICAR perfusion via osmotic pump and catheter). Importantly, we used slow-twitch soleus muscles for this experiment, hypothesizing that aged slow-twitch muscle (previously displaying neither elevated AMPK activity nor atrophy with age (Figure 1)[25] would exhibit sarcopenia-like properties if AMPK were chronically activated similar to aged fast-twitch muscle. As hypothesized, continuous AMPK activation elicited significant fiber atrophy in both young adult and old muscles (Figure 5). Moreover, an additional unexpected finding of continuously activating AMPK in resting muscle was a high frequency of fiber death

One week of continuous 5′-AMP-activated protein kinase (AMPK) activation causes fiber atrophy and death in slow-twitch soleus muscles of young adult (YA; 8 mo) and old (O; 30 mo) Fisher344 × Brown Norway F1 hybrid rats. Muscles were locally and continuously perfused (osmotic pump and catheter) with either 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; an AMPK activator) at 0.5 mg·h-1 or vehicle (saline) during the 1-wk period. Fiber cross-sectional area was significantly (P ≤0.05) reduced in both age groups (by 25% in YA muscles and by 24% in O muscles; n = 3 per group). Images are representative muscle cross-sections stained with hematoxylin and eosin.


One week of continuous 5′-AMP-activated protein kinase (AMPK) activation causes fiber atrophy and death in slow-twitch soleus muscles of young adult (YA; 8 mo) and old (O; 30 mo) Fisher344 × Brown Norway F1 hybrid rats. Muscles were locally and continuously perfused (osmotic pump and catheter) with either 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR; an AMPK activator) at 0.5 mg·h-1 or vehicle (saline) during the 1-wk period. Fiber cross-sectional area was significantly (P ≤0.05) reduced in both age groups (by 25% in YA muscles and by 24% in O muscles; n = 3 per group). Images are representative muscle cross-sections stained with hematoxylin and eosin.

The fiber atrophy induced by AMPK activation (Figure 5) agrees with findings that cultured myotube diameter is reduced under conditions in which AMPK activity is up-regulated[1] and supports the possibility that chronically elevated AMPK activity may contribute to basal fast-twitch fiber atrophy with age (sarcopenia). Suppression of muscle protein translation and synthesis[4,24] may be one mechanism by which AMPK exerts this effect; however, it is highly doubtful that solely suppressing protein synthesis would elicit the striking fiber atrophy and death observed in just 7 d (Figure 5). Thus, activation of protein degradation pathways is also a likely possibility. As previously mentioned, AMPK is known to stimulate muscle-specific lysosomal and proteasomal gene expression (FOXO, Atrogin-1, and MuRF1) as well as myofibrillar protein degradation.[15,17] The increased FOXO3A and MuRF1 mRNA expression and increased myofibrillar degradation with age in resting human muscle of mixed fiber types[21,28] may therefore result in part from elevated AMPK activity in the fast-twitch population. Interestingly, some have observed elevated rates of mixed[10] and myofibrillar[13] protein synthesis, along with higher S6K activation,[13] in aged rat fast-twitch muscle. Such a scenario would indicate a futile increase in protein synthesis rate in the face of an even faster degradation rate in these muscles, although still others have conversely observed lower basal protein synthesis in aged muscle.[29] Regardless of protein synthesis differences, an elevated protein degradation rate in aged fast-twitch muscle fibers likely plays a role in subtly, and over a long period of time, altering the synthesis-degradation balance toward gradual atrophy. We propose that chronically elevated AMPK activity may play a role in this phenomenon.

The possibility that continuously elevated AMPK activity affects the balance of myonuclear addition versus nuclear apoptosis in aged fast-twitch muscle is intriguing. Unfortunately, few data exist concerning AMPK's potential involvement in either phenomenon in skeletal muscle. Certainly, suppression of basal myonuclear addition cannot account for the rapidity with which AICAR induced fiber atrophy and death (Figure 5), and whether these effects were due to apoptotic mechanisms and/or more general fiber necrosis remains to be determined. However, AMPK does seem to play a key role in apoptotic signaling in mononucleated muscle cell types, including smooth muscle cells, cardiac myocytes, and immortalized (C2C12) skeletal myoblasts.[8,18] It is currently unclear whether AMPK is proapoptotic or antiapoptotic in these cells because there is somewhat equivocal evidence to support both.

In contrast to mononucleated cells, apoptosis in mature multinucleated skeletal muscle fibers does not necessarily mean fiber death but is more associated with fiber atrophy as the myonuclear domain volume remains relatively constant. It is unknown whether nuclear apoptosis leads to protein degradation and fiber atrophy or vice versa (i.e., fiber atrophy leads to nuclear apoptosis, which maintains a constant myonuclear domain volume). As might be expected, the frequency of apoptotic nuclei is well known to be increased in aged atrophying muscle fibers.[5] If AMPK is proapoptotic in mature muscle fibers similar to other muscle cell types under some conditions,[8] then chronically elevated AMPK activity (Figure 1)[25] may play a role in the age-related increase in apoptotic nuclei. In fact, we propose that any potential role of AMPK in aging multinucleated muscle fibers is more likely proapoptotic than antiapoptotic because of the following logic: 1) if myonuclear domain volume is to be kept constant, it is paradoxical to protect against nuclear death while selectively reducing protein synthesis and/or stimulating protein degradation; and 2) the potential antiapoptotic effects of AMPK in mononucleated cells is thought to enhance cell survival during times of brief energy deficit,[8] whereas apoptosis in multinucleated muscle fibers is more associated with atrophy than a risk of cell death (and lost nuclei can be replenished from the myogenic precursor cell pool when energy balance is restored). Moreover, although the extent of atrophy and/or nuclear apoptosis necessary to eventually achieve a "threshold" precipitating complete muscle fiber death is unknown, our data indicate a role for continuous AMPK activation in fiber atrophy and eventual fiber death, not fiber survival (Figure 5). Because fiber atrophy and death are also characteristics of sarcopenic muscle,[29] the potential role of AMPK in mediating apoptosis in aged skeletal muscle fibers, either directly or indirectly (via fiber atrophy and the loss of myonuclear domains) demands further exploration.

 

[Antigravity]

Correct- Fried Cheese,

But its a little more complex than that- Remember we (human subjects) are not constantly infusing muscles with AICAr, even once daily up-regulates AMPK for a shorter period of time. Remember, exercise also upregulates AMPK expression, and increases mitochondria count. Pulsatile bursts of AMPK are extremely beneficial.
However, in "real world" results- bodybuilders would turn into endurance athletes if continuously supplementing AICAr.

 

[crazyfool405]

" The drug appeared to change the physical composition of muscle, essentially transforming the tissue from sugar-burning fast-twitch fibers to fat-burning slow-twitch ones, "

Isn't that the opposite of what a bodybuilder wants.

yep oppisite of waht power lifters and body builders want.