Molecular Formula: C10H11N2
Molecular Weight: 159.21 g/mol
CAS number: 42464-96-0
Purity: greater than 98%
5-amino-1MQ, a variant of methylquinolinium, is a potent peptide inhibitor that targets the enzyme nicotinamide N-methyltransferase (NNMT) found in the cytoplasm of cells. This enzyme has been associated with conditions such as obesity and type 2 diabetes due to its role in managing cellular energy balance. By suppressing the activity of NNMT, significant health benefits such as weight reduction, decrease in fat mass and adipocyte size, and lower levels of cholesterol and glucose in the blood have been observed. Consequently, 5-amino-1MQ and similar methylquinolinium derivatives are being extensively studied for their potential as therapeutic agents for obesity and diabetes.
NNMT is a cytosolic enzyme that is prevalent in various cells across the body, with the highest concentrations found in liver and fat cells. Studies conducted on mice have revealed that elevated levels of NNMT correspond with reduced levels of GLUT4, a sugar transporter. GLUT4 is primarily found in striated muscle (both skeletal and cardiac) and fat cells and plays a crucial role in regulating blood sugar levels and the onset of diabetes.
Interestingly, GLUT4 is also associated with basal metabolic rate and the concepts of fast and slow metabolism. Individuals with naturally high levels of GLUT4, often referred to as having a "fast metabolism," burn more calories than those with low levels of GLUT4. Exercise has been found to stimulate the production of GLUT4, which explains why physical activity can aid in combating weight gain, high blood sugar levels, and insulin resistance. The intricate connection between GLUT4 and NNMT, and their collective influence on basal metabolism in mammals, has been a significant area of research. For instance, mice that produce high levels of GLUT4 are more sensitive to insulin and are less likely to develop type 2 diabetes. Conversely, mice with low GLUT4 levels exhibit significant insulin resistance.
In simple terms, NNMT slows down the rate at which the body uses calories, leaving them available for storage as fat or glycogen. Lower levels of NNMT reduce the conversion of nicotinic acid (NA) into 1-methylnicotinamide (1-MNA), which has two effects on metabolism. Therefore, administering an NNMT blocker like 5-amino-1MQ results in increased energy expenditure and decreased energy storage. When combined with the fact that lower NNMT levels also increase the expression of the GLUT4 transporter, the result is improved glucose clearance from the blood and increased energy metabolism. Studies in mice have shown a 7% reduction in body weight and a 30% reduction in fat mass over just 10 days of administering 5-amino-1MQ, without any changes in food intake.
Investigations on mice aged 24 months (which is considered old in the mouse lifespan) have shown that the use of an NNMT inhibitor leads to a significant increase in stem cell activation in their muscle tissue after an injury, compared to those in the control group. The treated mice have myofibers that are twice as large in cross-section and possess enhanced contractile strength. In fact, the healed muscle of the treated mice demonstrates 70% more contractile force than that of the control mice. The advantages of enhancing muscle stem cell production extend beyond merely speeding up repair rates after an injury. The stimulation of stem cells could aid elderly individuals in maintaining their independence for a longer period.
There is also evidence to suggest that an increase in NNMT expression is a common characteristic of muscle wasting disorders such as Duchenne Muscular Dystrophy, and that decreasing NNMT levels may help to alleviate the symptoms of some of these conditions. This is again linked to the ability of NNMT to inhibit stem cell growth and division. By reducing NNMT levels, compounds like 5-amino-1MQ may provide benefits in a variety of muscle-wasting conditions.
It's important to remember that NNMT inhibition results in increased levels of NAD+. By replenishing NAD+ levels via NNMT inhibition, compounds like 5-amino-1MQ have been shown to improve muscle function, heart pathology, and DMD in animal models. It appears that the improvement in mitochondrial function combined with decreases in inflammation and fibrosis, all related to increases in NAD+ levels, are the main drivers of these benefits.
A Potential Role for 5-Amino-1MQ in Cognition NAD+ is a critical compound in brain energy homeostasis. Depletion of NAD+ has been linked to a number of cognitive conditions, but is known to impact communication at the synaptic junction of neurons and at the neuromuscular junction where nerves connect to muscle tissue. Research in mice suggests that decreases in NAD+ levels can reduce synaptic transmission, impair muscle function, and impact overall cognitive function. Although 5-amino-1MQ has not been specifically tested in this setting, there is good reason to believe that the compound will have the same effect on NAD+ levels in the brain as it has elsewhere. This means that it could be used not just as a treatment for cognitive dysfunction, but as a potential nootropic to boost cognitive function in the average individual. Whether this bears out in research remains to be seen, but there is active interest in the potential cognitive benefits of 5-amino-1MQ.
E. Carvalho et al. "Adipose-specific overexpression of GLUT4 reverses insulin resistance and diabetes in mice lacking GLUT4 selectively in muscle" [PubMed]
P. Pssios "Nicotinamide N-Methyltransferase: More Than a Vitamin B3 Clearance Enzyme" [PubMed]
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