Tesofensine 500mcg (30 Capsules)

Tesofensine

Tesofensine (also called TE) is a novel norepinephrine, dopamine, and serotonin reuptake inhibitor (triple reuptake inhibitor) that was initially developed for the treatment of neurodegenerative diseases like Parkinson’s disease and Alzheimer’s disease. As it turns out, the benefits of tesofensine extend further to include increased weight loss, even for people who do not undergo dietary changes. Tesofensine is now in phase III clinical trials as a weight loss aid.

What is Tesofensine?

Tesofensine is a member of the class of medications known as “triple reuptake inhibitors.” It prevents the presynaptic reuptake of neurotransmitters norepinephrine, dopamine, and serotonin. This leads to an increase in the effects of these neurotransmitters.

Tesofensine is a member of the phenyltropane class of drugs, which were originally developed to reduce cocaine dependency. In fact, this class of drugs arose as a result of efforts to disassociate the stimulant properties of cocaine from the factors that cause it to be addictive. In other words, the phenyltropane drugs are designed to stimulate the central nervous system without creating addiction.

It should come as no surprise, given their origins, that compounds like tesofensine have profound effects on neurotransmission, particularly dopamine, which is responsible for reward and craving behaviors. Research shows that tesofensine has no potential for recreational abuse, suggesting that at least some of the goals of efforts to dissociate the properties of certain stimulants have been achieved[1].

How Does Tesofensine Work?

Given its ability to increase dopamine levels, tesofensine was originally developed for the treatment of Parkinson’s disease. During clinical trials, however, a significant “side effect” of weight loss was consistently noted. Because the compound proved to be inferior to existing medications in the treatment of neurodegenerative disease, but nearly twice as effective in promoting weight loss as any existing compound on the market, the decision was made to pivot to trials on weight loss[2].

The ability of tesofensine to increase levels of neurotransmitters in the brain does not directly account for its ability to increase satiety and feelings of fullness. Neither does this factor account for the hypothesized ability of tesofensine to alter energy balance and increase metabolism. At this point, the exact reason that tesofensine is such an effective weight loss agent remains unclear.

It was originally thought that tesofensine was a relatively balanced reuptake inhibitor, increasing levels of dopamine, norepinephrine, and serotonin in roughly equal proportions. This turns out to not be the case. After more extensive study, it was found that tesofensine is much more effective in boosting norepinephrine levels than serotonin levels. It is better at boosting both of those neurotransmitters than it is at boosting dopamine levels[3]. This difference may explain why the drug wasn’t particularly successful in the treatment of Parkinson’s disease.

Tesofensine activity is not, however, strictly limited to the neurotransmitters just described. Research shows that it is also an indirect potentiator of cholinergic neurotransmission. Of course, this is why the drug was originally of interest in Parkinson’s disease and suggests that its dopamine effects might be more nuanced than is currently understood. Tesofensine appears to promote cognition, learning, and memory via the cholinergic pathway. This pathway ultimately leads to increased BDNF levels in the brain[3]. BDNF stimulates neuron growth and has been shown in previous research to benefit people with depression, cognitive decline, and certain neurological conditions.

Tesofensine and Weight Loss

So, just how effective is tesofensine when it comes to weight loss? Phase IIB clinical trial results indicate that tesofensine produces about 12.8 kg (~28 pounds) of weight loss over six months when administered as a 1 mg dose to people who have a 300 kcal deficit in their diet. When compared to placebo, this is a 6-fold increase in weight loss[4]. Compared to currently available FDA-approved weight-loss medications, tesofensine is twice as effective. The average weight loss in all other clinical trials of currently available drugs was just 3-5 kg of reduction over 6 months. In other words, people lose twice as much weight with tesofensine as they do with any currently available weight-loss aid approved by the Food and Drug Administration.

Of course, it isn’t just the efficacy of tesofensine that makes it attractive as a weight loss agent. The compound is also easily administered by mouth just once per day. The side effect profile has also proved to be minimal in clinical trials, consisting mostly of dry mouth, headache, GI upset, and difficulty with sleeping. Both the dry mouth and difficulty sleeping show dose-dependent prevalence as well as attenuation over long-term use[4], [5]. So, it is possible to greatly mitigate these side effects by starting out on a low dose of tesofensine and then increasing it once attenuation has occurred.

Research shows that tesofensine produces the greatest weight loss when paired with dietary caloric restrictions and exercise. However, research shows that results can still be expected when tesofensine is taken and no differences in diet or exercise are encouraged. In one clinical trial, men treated with tesofensine lost weight despite the fact they were instructed to maintain their standard diet and levels of physical activity. These men lost 1.8 kg in two weeks when compared to placebo and reported higher feelings of satiety and fullness as well as decreased desire to eat. There was, additionally, evidence that men in the tesofensine arm of the study expended almost 5% more energy while they slept than those in the placebo arm. This correlates well with the additional finding that fat oxidation is increased by tesofensine[6].

One interesting aspect of tesofensine research in obesity has been the revelation that satiety appears to be centrally controlled and, perhaps, is harder to modify permanently than was once thought. The administration of tesofensine has a profound effect on satiety and hunger, thus greatly diminishing appetite. However, withdrawal of the drug, even after weight loss, results in an almost immediate return to baseline sensations. Reintroduction of tesofensine will suppress them again[7]. This suggests that appetite sensations are more permanent and ingrained than once thought and may, in fact, contribute to weight gain to a higher degree than once believe. In other words, it really

In the past, it has been noted that compounds affecting appetite generally lose their efficacy over time. The same is true of tesofensine, with its ability to stave off hunger diminishing (but never completely stopping) with prolonged use. That said, tesofensine shows drastically longer-lasting hypophagic effects than other weight reduction aids and, more importantly, shows substantial rebound to baseline after a short holiday. In other words, a short break from tesofensine restores its ability to suppress appetite and hunger[9]. No trials have been carried out looking at the long-term weight loss of cycled tesofensine, but there is good reason to believe that the drug, when cycled appropriately, may produce even greater weight loss than what has currently been observed.

Tesofensine and Pain Management

The use of antidepressant medications in pain management is not new. Tri-cyclic antidepressants were among the first drugs available for treating mood disorders and have long been known to reduce nociception (pain perception), particularly in conditions like fibromyalgia. Research shows that the anti-nociceptive (anti-pain) properties of standard antidepressants, which affect only serotonin and norepinephrine, are enhanced by the addition of dopamine boosting agents[12]. Thus, there is speculation that triple reuptake inhibitors like tesofensine may provide benefits in pain management.

Tesofensine and Safety

Anti-obesity drugs have a long history of cardiovascular side effects. Fen-Phen is probably the most famous of the diet pills to have caused serious cardiac issues (e.g., heart valve damage) and though things have improved since 1997 when Fen-Phen was removed from the market, anti-obesity drugs are still hard on the heart. Sibutramine, for instance, has been associated with major cardiovascular events and was itself eventually withdrawn from the market in 2010[13]. The result is a death of options for treating obesity and feelings of hopelessness among those who seek relief. Phentermine, one of the ingredients in Fen-Phen can be used safely for short periods of time, but its reputation has produced fear and thus most people and healthcare providers are unwilling to use it.

To date, tesofensine has shown a substantially improved risk profile compared to other anti-obesity drugs. In particular, its central action on neurotransmitter reuptake as opposed to peripheral action of lipase inhibitors, amphetamines, and other compounds makes tesofensine unique[14]. There was some argument about trial design and whether side effects of tesofensine had been under reported[15]. The claim is that investigators did not list people with headache, migraine, stress, and depression prior to treatment as having those side effects if they experienced it during treatment. This is a valid criticism of the study design because a distinction should have been made between existing symptoms and new, but similar, symptoms. A change in trial design would likely have had no major impact on tesofensine side effect reporting.

Tesofensine Overview

Tesofensine is a novel inhibitor of the reuptake of serotonin, norepinephrine, and dopamine. By increasing levels of all three of these neurotransmitters, tesofensine increases BDNF expression patterns and promotes neurogenesis in the amygdala. None of this explains why it is the most effective weight loss agent developed to date, however. Research shows that tesofensine is at least twice as effective as any currently approved weight loss agent and with far fewer (and far less serious) side effects. While research is ongoing to get tesofensine to market as an anti-obesity drug, there is deeper research being carried out to understand how this molecule affects the sensations of hunger and satiety to produce weight loss. While tesofensine is proving to be a remarkable weight loss agent, it may yet prove to be even more remarkable by helping to elucidate the connection between the human brain and gut that controls eating behavior to begin with. With that knowledge, science could virtually eliminate obesity.

Tesofensine exhibits minimal side effects, good oral and excellent subcutaneous bioavailability in mice. Per kg dosage in mice does not scale to humans. Tesofensine for sale at Peptide Sciences is limited to educational and scientific research only, not for human consumption. Only buy Tesofensine if you are a licensed researcher.

Storage Instructions:

All of our products are manufactured using the Lyophilization (Freeze Drying) process, which ensures that our products remain 100% stable for shipping 3-4 months reconstituted (mixed with bacteriostatic water) to maintain stability. After reconstitution, the peptides will remain stable for up to 30 days.

Lyophilization is a unique dehydration process, also known as cryodesiccation, where the peptides are frozen and then subjected to low pressure. This causes the water in the peptide vial to sublimate directly from solid to gas, leaving behind a stable, crystalline white structure known as lyophilized peptide. The puffy white powder can be stored at room temperature until you're ready to reconstitute it with bacteriostatic water.

Once peptides have been received, it is imperative that they are kept cold and away from light. If the peptides will be used immediately, or in the next several days, weeks or months, short-term refrigeration under 4C (39F) is generally acceptable. Lyophilized peptides are usually stable at room temperatures for several weeks or more, so if they will be utilized within weeks or months such storage is typically adequate.

However, for longer term storage (several months to years) it is more preferable to store peptides in a freezer at -80C (-112F). When storing peptides for months or even years, freezing is optimal in order to preserve the peptide’s stability.