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Research Chemical SciencesUGFREAKeudomestic
napsgeargenezapharmateuticals domestic-supplypuritysourcelabsResearch Chemical SciencesUGFREAKeudomestic

Espindolol: Anabolic Catabolic Transforming Agent- Inc. muscle mass; Dec Fat Mass

mrgodlike

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Found this pubmed link on another forum. Thought I would share it here. Maybe a future Research Chem ;)


Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany.
Abstract

BACKGROUND:
Sarcopenia, the age-related, progressive loss of skeletal muscle mass, strength, and function, is a considerable socioeconomic burden by increasing risks of falls, fractures, and frailty. Moreover, sarcopenic patients are often obese and therapeutic options are very limited.

METHODS:
Here, we assessed the efficacy of espindolol on muscle mass in 19-month-old male Wistar Han rats (weight, 555 ± 18 g), including safety issues. Rats were randomized to treatment with 3 mg/kg/day espindolol (n = 8) or placebo (n = 14) for 31 days.

RESULTS:
Placebo-treated rats progressively lost body weight (-15.5 ± 7.2 g), lean mass (-1.5 ± 4.2 g), and fat mass (-15.6 ± 2.7 g), while espindolol treatment increased body weight (+8.0 ± 6.1 g, p < 0.05), particularly lean mass (+43.4 ± 3.5 g, p < 0.001), and reduced fat mass further (-38.6 ± 3.4 g, p < 0.001). Anabolic/catabolic signaling was assessed in gastrocnemius muscle. Espindolol decreased proteasome and caspase-3 proteolytic activities by approximately 50 % (all p < 0.05). Western blotting showed a reduced expression of key catabolic regulators, including NFκB, MuRF1, and LC-3 (all p < 0.01). The 50- and 26-kDa forms of myostatin were downregulated fivefold and 20-fold, respectively (both p < 0.001). Moreover, 4E-BP-1 was reduced fivefold (p < 0.01), while phospho-PI3K was upregulated fivefold (p < 0.001), although Akt expression and phosphorylation were lower compared to placebo (all p < 0.05). No regulation of p38 and expression of ERK1/2 were observed, while phosphorylation of p38 was reduced (-54 %, p < 0.001) and ERK1/2 was increased (115 and 83 %, respectively, both p < 0.01). Espindolol did not affect cardiac function (echocardiography) or clinical plasma parameters.

CONCLUSION:
Espindolol reversed the effects of aging/sarcopenia, particularly loss of muscle mass and increased fat mass. Thus, espindolol is an attractive candidate drug for the treatment of sarcopenia patients.



Source Link:
http://www.ncbi.nlm.nih.gov/pubmed/?term=espindolol
 
Last edited:
Found this pubmed link on another forum. Thought I would share it here. Maybe a future Research Chem ;)


Applied Cachexia Research, Department of Cardiology, Charité Medical School, Berlin, Germany.
Abstract

BACKGROUND:
Sarcopenia, the age-related, progressive loss of skeletal muscle mass, strength, and function, is a considerable socioeconomic burden by increasing risks of falls, fractures, and frailty. Moreover, sarcopenic patients are often obese and therapeutic options are very limited.

METHODS:
Here, we assessed the efficacy of espindolol on muscle mass in 19-month-old male Wistar Han rats (weight, 555 ± 18 g), including safety issues. Rats were randomized to treatment with 3 mg/kg/day espindolol (n = 8) or placebo (n = 14) for 31 days.

RESULTS:
Placebo-treated rats progressively lost body weight (-15.5 ± 7.2 g), lean mass (-1.5 ± 4.2 g), and fat mass (-15.6 ± 2.7 g), while espindolol treatment increased body weight (+8.0 ± 6.1 g, p < 0.05), particularly lean mass (+43.4 ± 3.5 g, p < 0.001), and reduced fat mass further (-38.6 ± 3.4 g, p < 0.001). Anabolic/catabolic signaling was assessed in gastrocnemius muscle. Espindolol decreased proteasome and caspase-3 proteolytic activities by approximately 50 % (all p < 0.05). Western blotting showed a reduced expression of key catabolic regulators, including NFκB, MuRF1, and LC-3 (all p < 0.01). The 50- and 26-kDa forms of myostatin were downregulated fivefold and 20-fold, respectively (both p < 0.001). Moreover, 4E-BP-1 was reduced fivefold (p < 0.01), while phospho-PI3K was upregulated fivefold (p < 0.001), although Akt expression and phosphorylation were lower compared to placebo (all p < 0.05). No regulation of p38 and expression of ERK1/2 were observed, while phosphorylation of p38 was reduced (-54 %, p < 0.001) and ERK1/2 was increased (115 and 83 %, respectively, both p < 0.01). Espindolol did not affect cardiac function (echocardiography) or clinical plasma parameters.

CONCLUSION:
Espindolol reversed the effects of aging/sarcopenia, particularly loss of muscle mass and increased fat mass. Thus, espindolol is an attractive candidate drug for the treatment of sarcopenia patients.
Unfortunately, I read a whole lot of these research papers, and then you never hear anymore. The research is terminated, mostly because the "Big Pharma" company behind the research, doesn't think it's profitable enough to continue.
A case in point "Myostatin Inhibitors", originally researched back in 2005, looked promising in reducing Myostatin, which limits Muscle cell reproduction as you get older. The research was terminated because the research was limited in scope, and no one thought it might have an application in the Fitness Industry..........JP
 
interesting....wouldn't mind seeing more about this going forward.

and on a side note the Myostatin Inhibitors were also cancelled because they were just too damned expensive
 
interesting....wouldn't mind seeing more about this going forward.

and on a side note the Myostatin Inhibitors were also cancelled because they were just too damned expensive
That's the deal with all the research papers I've read. Big Pharma can't make a Billion Dollars, terminate the project........................JP
 
Just going to keep posting stuff I find.

From Patrick Arnold: http://patrickarnoldblog.com/espindolol-s-pindolol-mt-102/

Espindolol (S-Pindolol, MT-102)

Anabolic drugs are not dead, in fact research to develop new ones are aggressively being pursued to address medical situations such as cancer cachexia (wasting secondary to cancer) and sarcopenia (age related loss of muscle mass). Both of these categories are potentially huge money makers. Amongst the weird drugs that are being proposed for these applications is one that kind of boggles my mind. It is actually a current drug used to treat high blood pressure. Well, I guess you can say HALF of the drug is being developed as an anabolic


The drug I am referring to is called Pindolol, and the “half” that is being developed is S-pindolol. What I mean by that is that Pindolol is what is known as a racemic compound (it exists in a 50/50 ratio of right and left handed isomers) and the drug proposed as an anabolic is S-pindolol (the left handed isomer only). Many drugs are like this and often only one isomer is the active one. Take for example methamphetamine. Its active isomer is the right handed one. The left handed one is weak enough that it is allowed to be sold over the counter as a component of vicks inhalers.


Pindolol is sold to treat high blood pressure and it does so by blocking the effects of adrenaline like compounds on the heart (it’s a beta1 blocker). As such it decreases the force and frequency of heartbeats and thusly blood pressure decreases. Interestingly, pindolol also has agonist effects upon receptors of adrenaline like compounds too, specifically on skeletal muscle (it’s a beta2 agonist). You may be familiar with beta2 agonists such as clenbuterol. They are anabolic


Anyway, this compound (the S-isomer of pindolol which is the isomer that does stuff) is poised to be marketed as an anabolic for cancer cachexia and maybe sarcopenia. Studies have been done that have demonstrated muscle growth in these models. Myostatin has been shown to be suppressed amongst other things, which are effects we know happens with beta2 agonists (at least in the short term). Cool thing is that unlike most beta2 agonists (clen) this has no stimulatory effect on the heart. Not so cool thing is that it actually has a depressive effect on the heart, which means your exercise performance can suffer because your heart won’t beat fast and hard enough to support your efforts (that is if you train like a man)

Anyway, interesting stuff I suppose and expect it to appear on your banned list soon

Advances in understanding and treating cardiac cachexia: highlights from the 5th Cachexia Conference (http://www.ncbi.nlm.nih.gov/pubmed/20561693)

Int J Cardiol. 2010 Oct 29;144(3):347-9. doi: 10.1016/j.ijcard.2010.05.042. Epub 2010 Jun 19.
Advances in understanding and treating cardiac cachexia: highlights from the 5th Cachexia Conference.Advances in understanding and treating cardiac... [Int J Cardiol. 2010] - PubMed - NCBI
von Haehling S, Stepney R, Anker SD.

Abstract

Cardiac cachexia as a terminal stage of chronic heart failure carries a devastating prognosis. This article focuses on novel insights into the pathophysiology and on new treatment approaches to cardiac cachexia. Drugs that have been used in preclinical and clinical studies that may also confer beneficial effects in cardiac cachexia include but are not limited to the type 4 melanocortin receptor antagonist SNT 207979, the appetite promoting synthetic ghrelin SUN11031, the soluble myostatin decoy receptor ActRIIB-Fc, the fast skeletal muscle troponin activating substance CK-2017357, the anti-catabolic/anabolic transforming agent MT-102, the anti-inflammatory agent celecoxib, and testosterone supplementation.



The ACT-ONE trial, a multicentre, randomised, double-blind, placebo-controlled, dose-finding study of the anabolic/catabolic transforming agent, MT-102 in subjects with cachexia related to stage III and IV non-small cell lung cancer and colorectal cancer: study design. (http://www.ncbi.nlm.nih.gov/pubmed/22207908)

The ACT-ONE trial, a multicentr... [J Cachexia Sarcopenia Muscle. 2011] - PubMed - NCBI
Stewart Coats AJ, Srinivasan V, Surendran J, Chiramana H, Vangipuram SR, Bhatt NN, Jain M, Shah S, Ali IA, Fuang HG, Hassan MZ, Beadle J, Tilson J, Kirwan BA, Anker SD; on behalf of the ACT-ONE Trial Investigators.

Abstract

AIMS: Cachexia, the wasting disorder associated with a wide range of serious illnesses including cancer, is a major cause of morbidity and mortality. There is currently no widely approved therapeutic agent for treating or preventing cancer-associated cachexia. Colorectal cancer and non-small cell lung cancer have relatively high incidences of cachexia, approximately 28% and 34%, respectively. Neurohormonal overactivity has been implicated in the genesis and progression of cachexia and beta receptor antagonism has been proposed as a potential therapy. MT-102, a novel anabolic/catabolic transforming agent, has a multi-functional effect upon three potential pharmacological targets in cancer cachexia, namely reduced catabolism through non-selective β-blockade, reduced fatigue, and thermogenesis through central 5-HT1a antagonism and increased anabolism through partial β-2 receptor agonism.

METHODS: At least 132 male and female patients, aged between 25 and 80 years with a confirmed diagnosis of late-stage non-small cell lung cancer or colorectal cancer, with cachexia will be randomised to either one of the two MT-102 doses or placebo in a 3:1:2 ratio (MT-102 10 mg BD(-1)/MT-102 2.5 mg BD/placebo). Patients will continue on study treatment for maximally 16 weeks. The primary endpoint, to be analysed by assigned treatment group, will be body weight change over 16 weeks. For this endpoint, the study has 85% power (0.05% significance level) to detect per 4-week period a mean change of -0.8 kg in the placebo group and 0 kg in the high-dose MT-102 arm. The first patient was randomised in February 2011 and patient recruitment is expected to continue until mid-2012.

PERSPECTIVE: The ACT-ONE trial is designed to test whether the anabolic/catabolic transforming agent MT-102 will positively impact on the rate of change of body weight in cancer cachexia, thereby evaluating a novel therapeutic strategy in this hitherto poorly treatable condition. A separate ACT-TWO trial will recruit patients who complete the ACT-ONE trial and remain on randomised double-blind medication. Participants in ACT-TWO will be followed for an additional period with a separate primary endpoint.
 
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