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The History of SARMs

The History of SARMs

SARMs have been a hot topic in the fitness industry for years. These potent compounds promise muscle growth beyond what athletes and bodybuilders could achieve naturally, enhancing their results.

But where did they come from and how did they emerge? That’s the topic of this post. It explores the history of SARMs (selective androgen receptor modulators) and how they came to be so immensely popular.

Early Science: 1935 to 1998

The first half of the twentieth century was a golden era for medical discovery. Researchers isolated insulin and discovered penicillin and streptomycin (two classes of antibiotics), and painkillers like lidocaine.

It was in this environment that researchers first isolated testosterone – a precursor to modern SARMs. The lab version of the hormone appeared to mimic the body’s natural version, leading to muscle mass increases, acne, hoarseness, and mood swings.

By 1939, medical practitioners were using testosterone in patients. However, it wasn’t selective. Synthetic versions seemed to target all receptors in the body, not just those that might help the patient.

During the 1930s, scientists also discovered 17α-alkylated anabolic steroids. These absorbed into the body better when taken in pill form but also suffered from lack of selectivity. Again, they activated all receptors, affecting muscle growth and sexual characteristics.

Researchers first synthesized nandrolone in 1950. Some consider it the first SARM because of its partial selectivity. It is still an anabolic steroid but appears to affect the bones and muscles more than other tissues (which is why many athletes use it as a performance-enhancing drug).

During the 1970s, non-steroidal AR antagonists emerged, like flutamide and bicalutamide. These bind to androgen receptors (ARs), preventing pro-androgenic activity while preserving desirable anabolic effects.

Researchers introduced these compounds for their therapeutic applications in cancer care. The drugs could block testosterone’s action on tumors, reducing their ability to grow.

This concept was arguably the inspiration for SARMs. The idea you could selectively block androgen activity paved the way for testosterone-like drugs that could minimize unwanted, off-target side effects.

However, it’s important to note that non-steroidal AR antagonists are not SARMs. These drugs (like flutamide) block the activity of various ARs while SARMs activate them – which is the opposite. 

The target tissue focus is also different. AR antagonists don’t attempt to target specific organs (or prevent interactions with others) as SARMs do.

Emergence: 1998 to 2005

Researchers developed the first non-steroidal SARMs in 1990, adopting the name from a previous class of drugs called SERMs (selective estrogen receptor modulators). Excitingly, these drugs induced anabolic activity in muscle and bone tissue while sparing the liver and prostate.

For SARMs, 1998 was a breakthrough year. Teams at the University of Tennessee and Ligand Pharmaceuticals created compounds independently offering this selective activity.

The University of Tennessee made aryl-propionamide SARM, defined by its core chemical structure containing an aryl group. Researchers were excited by arylpropionmaides’ ability to promote muscle and bone growth while bypassing the prostate and seminal vesicles, making it a candidate drug for osteoporosis and sarcopenia patients.

Ligand Pharmaceuticals developed its drugs around tricyclic quinolinones. Again, these targeted androgen receptors selectively. Furthermore, they activated the prostate minimally, reducing disease risk.

From 1998 to 2005, SARM manufacturers and researchers focused on creating new chemical structures or scaffolds for their drugs. Researchers experimented with modifications to these networks to yield more desirable effects.

Building SARMs to encourage muscle and bone growth was the main focus at this time. Researchers wanted to tackle muscle-wasting diseases and saw selective androgen drugs as a way to do it without causing intolerable side effects.

Many drugs entered pre-clinical trials with researchers looking for effects in animal models and how these might transfer to humans. Petri dish experiments on cell cultures also shed light on more details about the mechanism SARMs use to exert their effects on the body.

For example, aryl-propionamide SARMs showed promise for increasing muscle mass in castrated rats without broader side effects. On autopsy, the seminal vesicles and prostate appeared normal.

Ligand pursued SARM development with one molecule advanced to stage I clinical trials. However, it stopped abruptly and hasn’t published new data since.

Even so, other large pharmaceutical companies continued to progress the science during the late 1990s and early 2000s. Pfizer, Orion, Johnson and Johnson, Glaxo, and Merck continued to develop their drugs and ready them for market. Research from the period indicated tissue selectivity and anabolic activity, but these early compounds failed to develop further. Some were toxic and others were ineffective when used in vivo.

During this period, researchers tried to detect the underlying mechanisms for SARM tissue selectivity. Scientists wanted to know why these drugs were so effective.

One theory says that SARMs use coactivators and corepressors, or “helper proteins,” that block or boost AR signaling depending on the tissue. The idea was that there was full activation in the bone and muscle and minimal activation in the prostate. Steroids on the other hand, only rely on corepressors, preventing them from modulating their effects as much.

Another theory argued that the key to the puzzle lay in the properties of enzymes. The hypothesis suggested that enzymes break down conventional anabolic steroids into even more potent metabolites but SARMs, being non-steroidal, don’t.

Finally, scientists thought there might be some hidden signaling pathways SARMs use to communicate with cells that steroids don’t. Teams found that it might depend on the shape of the AR protein or the speed with which SARMs move in and out of the cell nucleus.

Ultimately, 1998 to 2005 laid the groundwork for the introduction of more effective SARMs. The principle that you could selectively activate tissue seemed solid; it was just a matter of putting it into action.

Recent Developments: 2006 to Present

Of course, the development of SARMs didn’t stop after 2000. Researchers recognized they were onto something and were keen to explore the topic further.

One area of interest was SARMs’ alleged ability to reduce fat mass. Scientists found that it could help people and animals lose weight.

Like modern semaglutide, SARMs appear to influence appetite-regulation hormones like ghrelin or leptin. The presence of testosterone may alter these signaling compounds, causing individuals to feel fuller than they are.

Some researchers also think there might be some SARM-specific effects. For example, SARMs might also suppress appetite direction through unknown actions.

Unfortunately, the research in this area is still limited, even in the current era. While progress is being made, scientists are still piecing together the metabolic pathways that regulate appetite and trying to determine how SARMs might play a role.

To make matters more challenging, there are also confounding factors. Many people using SARMs are also on strict exercise and diet routines that may also foster a reduction in fat mass.

Whether new and comprehensive SARM research is undertaken depends partly on decisions by the Food and Drug Administration (FDA). The government body currently considers them unapproved drugs because they haven’t been through the rigorous testing it requires.

Currently, researchers are exploring the potential impact of SARMs across a range of diseases. For example, SARMs show some promise in reversing the bone loss seen in osteoporosis compared to existing reabsorptive therapies. Novel compounds may enable the body to retain more bone mineralization, consistent with animal studies and earlier research from the 2000s.

Alzheimer’s disease may be another target for these drugs. Testosterone depletion often accompanies dementia, potentially harming brain function. SARMs can bind to these brain receptors, leading to improvements in cognitive function.

Increased androgen levels might also improve breast cancer outcomes. SARMs can interact with breast tissue ARs, offering benefits without causing women to develop masculine characteristics as a side effect.

Further applications could apply in prostate cancer. SARMs might act like androgen antagonists or induce cancer cell death – a process called apoptosis. Certain compounds could provide relief from enlarged prostate symptoms, making it easier for men to pee.

SARMs could even represent the emergence of male contraception. Some SARM-related compounds show promise in animal studies, appearing to offer reversible repression of fertility. However, more research is needed. 

Other uses of SARMs highlighted in recent literature include:

  • Treating stress-related urinary incontinence (SUI) by improving pelvic floor muscle mass (an initial phase II clinical trial failed to show significant results)
  • Addressing benign enlarged prostate symptoms by avoiding the formation of testosterone metabolite DHT
  • Improved treatment of hypogonadism (small genitals) and improvements in sexual desire
  • Targeting the muscle-wasting effects of Duchenne muscular dystrophy (DMD)

Currently, treatments for these medical issues are still in the clinical trial phase and no FDA-approved SARM drugs are available from doctors. However, the compounds are still being used in research settings with scientists hoping to make breakthroughs to make patients’ lives better.

Wrapping Up

So, that’s the history of SARMs, from their beginnings in the 1930s until the most recent science in the present. The drugs show immense promise but trials are ongoing. Whether the FDA will approve any of them for any condition remains to be seen. 

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