5-Amino-1MQ

Overview of 5-Amino-1MQ

The molecule 5-amino-1methylquinolinium (5-amino-1MQ) is a structurally compact analogue of methylquinolinium that functions as a selective inhibitor targeting the peptide-based enzyme nicotinamide N-methyltransferase (NNMT) in the cytosol. Scientific studies have established links between NNMT enzyme activity and metabolic disorders such as obesity and type 2 diabetes, with this enzyme playing a critical role in cellular energy balance. Blocking NNMT results in remarkable outcomes: significant weight reduction, decreased fat mass and reduced adipocyte dimensions, alongside improved cholesterol and glucose plasma markers. Currently, 5-amino-1MQ and related methylquinolinium compounds are being studied as promising therapeutic options for weight control and diabetes management. Evidence also suggests that NNMT inhibition may activate stem cells and enhance regenerative function in skeletal muscle tissue.

Chemical Structure of 5-Amino-1MQ

Molecular Formula: C₁₀H₁₁N₂
Molecular Weight: 159.21 g/mol

Source: pubchem

Scientific Research on 5-Amino-1MQ

Applications in Obesity

We currently face a global health crisis with obesity, a condition initially common in wealthy nations but now prevalent worldwide among both men and women. Research across many studies demonstrates that elevated NNMT concentrations are linked with metabolic problems. This enzyme has been connected to lipid storage mechanisms and diabetes advancement. In rodent studies, mice generating high GLUT4 levels are leaner, healthier, and exhibit improved insulin response. Conversely, diabetic mice with high fat content and low GLUT4 levels demonstrate profound insulin resistance.

Mouse model studies show that excess body weight stems from metabolic imbalance and unusually elevated NNMT enzyme levels, leading to moderate weight gain. This elevation stimulates NAD+ (Nicotinamide Adenine Dinucleotide), reducing the requirement for GLUT4. As GLUT4 levels drop, insulin resistance emerges, accelerating weight accumulation and obesity. Studies report that in test subjects displaying weight gain, inhibiting NNMT demonstrates therapeutic promise for weight control. Research indicates that treating diabetic and obese mice with low GLUT4 levels shows improved conditions with NNMT inhibitors, including in animals with natural resistance. Manipulating this pathway has demonstrated progress in managing obesity and insulin resistance, thus impacting diabetes. In one study, overweight rodents exposed to NNMT inhibitory compounds exhibited all characteristics of metabolic excellence. Human metabolism normally operates with high efficiency. Unfortunately, this very efficiency may work against efforts to diminish weight gain, making interventions more challenging when caloric intake is excessive. Understanding the genetic and molecular mechanisms underlying our propensity for obesity during excess calorie intake will likely reveal additional causes. Decreasing NNMT, given its relationship with GLUT4, may be the link scientists have been searching for.

In basic terms, NNMT determines how rapidly the body absorbs calories, making them available for storage as fat or glycogen. Decreased NNMT increases inhibition of this enzyme, causing SAM (S-adenosyl methionine) to be used in alternative pathways. This has two metabolic effects:

[DIAGRAM: Metabolic pathway showing NAD+, NNMT, SAM interactions and their effects on fat storage and insulin]

Source: Science Brief

The net result of administering an NNMT blocker like 5-amino-1MQ is an increase in metabolic efficiency with decreased energy storage. When coupled with SAM's role in cellular aging processes, this provides another excellent reason for improvements in glucose metabolism and blood markers. Research also discovered potential benefits to liver function and energy levels. In rat studies, white adipose tissue (WAT) decreased by approximately 3%, while cholesterol decreased by about 7% over seven weeks. NAD+ levels showed 3-7% boosts from 5-amino-1MQ usage within 30 days without any changes in food intake—meaning mice maintained normal eating patterns while showing improved body composition regarding stored adipose tissue. Over six weeks, these mice had various improvements including enhanced insulin sensitivity and increased action of factors like PPAR-alpha, a trigger for fat turnover and cell replication.

Source: Science Brief

Specialized lipids termed FAHFAs (fatty acid hydroxyl fatty acids) provide improved insulin sensitivity and facilitate glucose entry into muscle cells through PPAR-alpha signaling. Most crucial evidence suggests that 5-amino-1MQ's effects may extend beyond its ability to downregulate NNMT and thus increase insulin action and glucose uptake into cells by: (1) increasing NAD+ molecules that enable cells to produce an alternative class of lipids with outstanding anti-diabetic and anti-inflammatory characteristics.

5-Amino-1MQ and Skeletal Muscle Function

The impact of 5-amino-1MQ on skeletal muscle is multifaceted. Much like in adipose tissue, this compound affects muscle energetics and may lead to mitochondrial generation (power plants within cells creating energy).

Recent research suggests that inhibiting NNMT in any way, including with 5-amino-1MQ, may actually have direct effects on muscle structure and function.

Research in mice shows that after just four weeks, those treated with an NNMT inhibitor experienced considerable muscle cell activation within the body, activating muscle growth proteins. When treated with NNMT inhibition, aging muscles were remarkably improved with increased muscle protein content—up to 70% in some cases. More tellingly, these changes started within days of 5-amino-1MQ administration, suggesting rapid activation of muscle-building processes even in diabetic animals.

These results showed elevated NAMPT levels, and reducing NNMT levels leads to more powerful effects on fat mass. By improving vitality and decreasing activation of sarcopenic (muscle-degrading) proteins such as ubiquitin ligase MuRF1, NNMT inhibition helps aging and diabetic animals maintain and repair muscle tissue. This stimulation helps individuals preserve their existing muscle mass, suggesting a potential role in treatment of conditions like muscular dystrophy and muscle wasting that results from age.

The actual mechanisms by which NNMT inhibitors affect muscle function are not fully understood, but another factor appears to relate to NAD+ levels. Recall that NAD+ acts as a catalyst for various cellular processes. Compounds like 5-amino-1MQ have been shown to improve muscle function, heart pathologies, and IGF1 in several studies, in addition to metabolic effects seen in mice. These models and earlier studies suggest that 5-amino-1MQ's benefits, related to increases in NAD+ levels, represent one of several beneficial compound classes.

A Possible Role for 5-Amino-1MQ in Cognitive Function

NNMT is a critical component in cellular energy expenditure. Depletion of NAD+ has been shown to produce impairment in brain energy activity, leading to decreased cognition. Studies show defects in neurogenesis (the development of new neurons) and reduced synaptic function at neuromuscular junctions where neurons connect to muscle fibers. Research in mice suggests that inhibition of NAD+ creates severe failure in various brain regions, leading to severe loss in cognitive function.

Though 5-amino-1MQ has not been specifically tested in this setting, there is good reason to believe that the compound, through its NAD+-related effects, may provide benefits. More significantly, there is evidence that restoration of NAD+ to neuronal structures creates improvements in cognitive dysfunction and potential increases in overall brain cognitive function. Studies also indicate brain health benefits, though comprehensive understanding remains to be established. There is active rationale for exploring the potential cognitive benefits of 5-amino-1MQ.

Significant research suggests that NNMT expression is increased in gastric cancer.

5-Amino-1MQ Summary

5-amino-1MQ is a groundbreaking compound that inhibits the enzyme nicotinamide N-methyltransferase. It has been shown in animal models to result in substantial weight reduction and preferential fat loss. NNMT is associated with metabolic diseases such as obesity and diabetes; therefore, inhibiting NNMT with 5-amino-1MQ can lead to weight reduction, diminished adiposity, and improved metabolic function. Laboratory animal research demonstrates that inhibiting NNMT with 5-amino-1MQ can lead to significant changes in body composition over the course of treatment—resulting in weight loss and improved muscle function. There is hope that compounds like 5-amino-1MQ may play a role in treating conditions like muscular dystrophy and muscle wasting that results from age.

In summary, 5-amino-1MQ is a selective NNMT inhibitor with excellent promise as we continue to advance our understanding of obesity treatment and metabolic disease management.