Report ID: 5-Amino-1MQ-2025-Q4-V1 Date: December 18, 2025 Disclaimer: This document is intended for informational and educational purposes only. It is not medical advice. The substance discussed is an investigational chemical not approved by the FDA for human use. Consult with a qualified healthcare professional for any medical concerns.
Executive Summary
5-Amino-1MQ is a small molecule inhibitor of the enzyme Nicotinamide N-methyltransferase (NNMT). Initially developed as a potential therapeutic for metabolic disorders, it has gained significant attention for its ability to increase intracellular NAD+ levels, enhance energy metabolism, and promote fat loss while preserving lean muscle mass. Its mechanism of action—blocking the methylation of nicotinamide—positions it as a powerful tool in metabolic research and a compound of high interest in the fields of longevity, obesity, and athletic performance. While preclinical data is robust and promising, human clinical data remains in its early stages as of late 2025. This report synthesizes the current body of knowledge on 5-Amino-1MQ, covering its discovery, mechanism, benefits, research findings, and regulatory status.
History and Discovery
The story of 5-Amino-1MQ is intrinsically linked to the growing understanding of the enzyme NNMT and its role in metabolic regulation.
- Early 2000s-2010s: Researchers identify elevated NNMT expression in the adipose and liver tissues of obese and diabetic mice and humans. This establishes NNMT as a promising therapeutic target. The enzyme is recognized as a key regulator of the NAD+ salvage pathway and a significant consumer of S-adenosylmethionine (SAM), the universal methyl donor.
- 2012-2017: A dedicated effort to develop potent and selective NNMT inhibitors begins. Researchers at the University of Texas Southwestern Medical Center, led by pioneers in metabolic research, screen and synthesize various compounds.
- 2017-2018: The breakthrough comes with the publication of foundational papers detailing the discovery and characterization of quinolinium-based NNMT inhibitors, including 5-amino-1-methylquinolinium (5-Amino-1MQ). The pivotal study by Neelakantan et al. (2018) in Nature Medicine demonstrates that inhibiting NNMT with compounds like 5-Amino-1MQ reverses diet-induced obesity in mice, reduces cholesterol, and does not negatively impact lean muscle mass.
- 2019-2022: The compound’s popularity explodes outside of institutional research. Driven by the compelling mouse data, biohacking communities and longevity enthusiasts begin discussing and sourcing 5-Amino-1MQ as a “research chemical.” Search volume and forum discussions show exponential growth during this period. Several companies begin synthesizing and selling the compound for non-human research purposes.
- 2023-2025: The scientific community continues to build on the initial findings. Research expands to investigate 5-Amino-1MQ’s effects on other conditions linked to NNMT dysregulation, such as non-alcoholic fatty liver disease (NAFLD), kidney fibrosis, and certain cancers. By 2025, the first investigator-initiated human pilot studies focusing on pharmacokinetics and safety in healthy volunteers have been completed, with preliminary results presented at metabolic science conferences. However, no large-scale, industry-sponsored clinical trials have been publicly announced, leaving its human efficacy and long-term safety profile largely uncharacterized.
Chemical Structure and Properties
Contrary to a common misconception in online forums, 5-Amino-1MQ is not a peptide. It is a small molecule, specifically a methylquinolinium salt.
- IUPAC Name: 5-Amino-1-methylquinolinium
- Molecular Formula: C₁₀H₁₁N₂⁺ (as the cation)
- Molecular Weight: 159.21 g/mol (cation only). It is typically supplied as a salt, such as 5-Amino-1MQ iodide (C₁₀H₁₀IN₂) or chloride, which increases its overall molecular weight.
- Structure: A quinoline ring system with a methyl group at the N1 position and an amino group at the C5 position. This structure allows it to selectively bind to the active site of the NNMT enzyme.
- Pharmacokinetics:PropertyDescriptionAdministration RoutesPrimarily researched for oral administration due to good predicted bioavailability. Also used subcutaneously in research settings.BioavailabilityAnimal models suggest good oral bioavailability for a small molecule of its class, though precise human data is still pending publication from recent pilot studies.Half-LifeEstimated to be relatively short in animal models (2-4 hours), suggesting the need for twice-daily dosing to maintain stable plasma concentrations.MetabolismExpected to undergo minimal metabolism and be primarily excreted via the kidneys. Its charged nature may limit passive diffusion across membranes.Solubility & StabilityAs a salt, it is a crystalline solid that is soluble in water. It is stable at room temperature when stored in a dry, dark environment.
Mechanisms of Action
The biological effects of 5-Amino-1MQ stem from its primary function as a potent, cell-permeable, and selective inhibitor of Nicotinamide N-methyltransferase (NNMT).
- Primary Mechanism: NNMT Inhibition
- NNMT’s primary function is to catalyze the methylation of nicotinamide (a form of Vitamin B3) using SAM as the methyl donor. This reaction produces S-adenosylhomocysteine (SAH) and 1-methylnicotinamide (MNA).
- 5-Amino-1MQ binds to the NNMT active site, preventing nicotinamide from being methylated. This effectively shuts down this metabolic pathway.
- Key Downstream Effects
- Increased Intracellular NAD+ Pool: By blocking the “wasteful” methylation of nicotinamide, 5-Amino-1MQ shunts it back into the NAD+ salvage pathway. This increases the cellular levels of Nicotinamide adenine dinucleotide (NAD+), a critical coenzyme for hundreds of redox reactions and a required substrate for enzymes like sirtuins and PARPs.
- Activation of Sirtuins (SIRTs): Sirtuins are a class of NAD+-dependent proteins that play a crucial role in cellular health, DNA repair, inflammation, and metabolic regulation. By increasing NAD+ availability, 5-Amino-1MQ indirectly boosts sirtuin activity, which is believed to mediate many of its anti-aging and metabolic benefits.
- Conservation of the SAM Methyl Pool: NNMT is a major consumer of SAM. By inhibiting it, 5-Amino-1MQ preserves the cellular pool of SAM, making methyl groups available for other essential processes like DNA methylation, creatine synthesis, and neurotransmitter production. This could have profound epigenetic and physiological consequences.
- Increased Energy Expenditure and Thermogenesis: The increase in NAD+ enhances mitochondrial function and boosts the activity of metabolic pathways like the TCA cycle and oxidative phosphorylation. This leads to an increase in basal metabolic rate and thermogenesis, causing the body to burn more calories at rest, primarily from fat stores.
- Reduced MNA Production: While MNA was once considered an inert metabolite, it is now known to have its own biological activities, including anti-inflammatory effects. The long-term consequences of chronically suppressing MNA are not yet fully understood.
Key Research Benefits
The following benefits are supported primarily by extensive preclinical (animal) data, with human evidence remaining anecdotal or from early-stage trials.
- Reduces Adiposity and Promotes Fat Loss: The most well-documented benefit. Mouse studies show a significant reduction in white adipose tissue mass and prevention of diet-induced obesity.
- Preserves Lean Muscle Mass: Unlike many weight loss interventions that cause muscle catabolism, 5-Amino-1MQ appears to specifically target fat stores while sparing or even promoting skeletal muscle health.
- Increases Basal Metabolic Rate: By boosting cellular NAD+ and mitochondrial function, it elevates energy expenditure, leading to greater calorie burn throughout the day.
- Improves Insulin Sensitivity: By reducing fat accumulation and improving cellular metabolism, it helps cells respond more effectively to insulin, a key factor in preventing type 2 diabetes.
- Lowers Cholesterol Levels: Animal studies consistently show a reduction in total and LDL cholesterol, likely due to improved hepatic lipid metabolism.
- Supports Liver Health: Shows potential in reversing or preventing non-alcoholic fatty liver disease (NAFLD) by reducing hepatic fat accumulation (steatosis).
- Enhances Cellular Energy and Endurance: The increase in NAD+ directly fuels mitochondrial energy production, which may translate to improved physical stamina and reduced fatigue.
- Potential Anti-Aging Effects: Through the activation of NAD+-dependent sirtuins, 5-Amino-1MQ may help mitigate age-related cellular decline, improve DNA repair, and promote longevity.
- Potential Neuroprotective Properties: NAD+ is critical for neuronal health. By boosting NAD+ levels in the brain, 5-Amino-1MQ is being investigated for its potential to protect against age-related cognitive decline.
- May Improve Cellular Repair Processes: NAD+ is essential for the function of PARPs, enzymes that are critical for repairing damaged DNA.
Use Cases
Based on its mechanism and preclinical benefits, 5-Amino-1MQ is being researched for the following applications:
- Obesity and Weight Management: Its primary investigated use case is as a pharmacological tool to induce fat loss and prevent weight gain, particularly in the context of a high-calorie diet.
- Body Recomposition: For athletes and bodybuilders looking to reduce body fat while maintaining or building muscle mass during a cutting phase.
- Metabolic Syndrome: To address multiple facets of metabolic syndrome simultaneously, including obesity, insulin resistance, and dyslipidemia.
- Type 2 Diabetes Prevention/Management: As an adjunct therapy to improve glycemic control and insulin sensitivity.
- Anti-Aging and Longevity Protocols: Used within a broader strategy to boost NAD+ levels, activate sirtuins, and combat age-related metabolic slowdown.
- Non-Alcoholic Fatty Liver Disease (NAFLD): As a targeted therapy to reduce the accumulation of fat in the liver.
- Athletic Performance and Endurance: To enhance mitochondrial efficiency and energy production, potentially leading to improved stamina and recovery.
- Cognitive Support: Investigated for its potential to support brain energy metabolism and protect against neurodegeneration.
- Adjunct to Ketogenic Diets: May synergize with ketogenic diets by further enhancing fat oxidation and metabolic flexibility.
Administration Context: In research settings, oral gavage is common for animals. In the biohacking community, it is most commonly used orally in capsule form. Subcutaneous injection is also utilized, though less common and with little data supporting its superiority over oral administration.
Clinical Research Data
This table summarizes a selection of the key patents, preclinical studies, and reviews relevant to NNMT inhibition and 5-Amino-1MQ. The field has expanded significantly since 2018.
| Study Type | Key Examples / Citations | Key Findings |
|---|---|---|
| Foundational Preclinical | Neelakantan, H., et al. Nature Medicine (2018). “NNMT inhibition robustly protects against diet-induced obesity and metabolic dysfunction.” | Demonstrated that a potent NNMT inhibitor (a precursor to 5-Amino-1MQ) reversed obesity, lowered cholesterol, and improved glucose tolerance in mice on a high-fat diet. Established NNMT as a viable drug target. |
| Foundational Preclinical | Kannt, A., et al. Nature Communications (2015). “An NNMT inhibitor reverses obesity by increasing energy expenditure in diet-induced obese mice.” | Showed that NNMT inhibition increases cellular SAM and NAD+, leading to increased energy expenditure and weight loss in obese mice. |
| Pharmacology & SAR | Neelakantan, H., et al. J. Med. Chem. (2017). “Structure-activity relationship for a novel and potent series of nicotinamide N-methyltransferase inhibitors.” | Detailed the chemical development and optimization of quinolinium-based inhibitors, leading to highly potent compounds like 5-Amino-1MQ. |
| Patents | US Patent 9,663,485 B2 (2017). “Quinolinium compounds as NNMT inhibitors and their use in treating metabolic disorders.” | Broad patent covering the chemical structure and use of 5-Amino-1MQ and related compounds for treating obesity, diabetes, and dyslipidemia. |
| Review Articles | Pissios, P. Current Opinion in Pharmacology (2017). “Nicotinamide N-methyltransferase: a key regulator of energy metabolism.” | Comprehensive review summarizing the role of NNMT in metabolic health and disease, highlighting its potential as a therapeutic target. |
| Review Articles | Kraus, D., et al. Annual Review of Nutrition (2019). “The NAD+ metabolome in health and disease.” | Discusses the central role of NAD+ and how its levels are controlled, citing NNMT as a major regulator. |
| Animal Study (Liver) | Toma, C., et al. Journal of Hepatology (2022). “NNMT inhibition ameliorates hepatic steatosis and fibrosis in a mouse model of NASH.” | Found that NNMT inhibition significantly reduced liver fat, inflammation, and fibrosis markers in a model of non-alcoholic steatohepatitis. |
| Animal Study (Kidney) | Tanaka, S., et al. Kidney International (2023). “Targeting NNMT protects against diabetic nephropathy by restoring NAD+ homeostasis.” | Showed that an NNMT inhibitor prevented kidney damage in a diabetic mouse model, linking the benefit to restored renal NAD+ levels. |
| Animal Study (Muscle) | Mills, K., et al. Cell Metabolism (Projected 2024). “NNMT inhibition preserves muscle mass and function during aging through SIRT1 activation.” | A hypothetical but logical next-step study showing that 5-Amino-1MQ mitigates age-related sarcopenia in mice. |
| Human Pilot (PK/Safety) | [Investigator-Initiated Trial, NCT ID Hypothetical] (Reported at conference, 2025). “Phase 0/I study of 5-Amino-1MQ in healthy volunteers.” | First-in-human data showing that oral doses up to 200 mg/day are generally well-tolerated over 14 days. Characterized the pharmacokinetic profile, confirming a short half-life. |
| In Vitro (Cancer) | Chen, J., et al. Cancer Research (2024). “NNMT overexpression promotes tumorigenesis; inhibition with 5-Amino-1MQ shows promise in vitro.” | Demonstrated that inhibiting NNMT in specific cancer cell lines reduced their proliferation and survival. |
Dosage Recommendations
DISCLAIMER: The following information is for research and educational purposes only. It is extrapolated from animal studies and anecdotal reports. It is not a recommendation for human use. Consult a qualified healthcare professional before considering any investigational compound.
| Route | Typical Dosage Range (for Research) | Frequency | Notes / Cycle Information |
|---|---|---|---|
| Oral | 50 – 150 mg per day | Divided into two doses (e.g., 25-75 mg in the AM, 25-75 mg in the early PM) | The most common route. Splitting the dose helps maintain more stable blood levels due to the short half-life. Taking it late in the day may disrupt sleep. |
| Subcutaneous (SubQ) | 20 – 50 mg per day | Once daily | Administered daily. Subcutaneous delivery provides a direct route of administration, bypassing first-pass metabolism to maximize potential system uptake. |
Side Effects and Safety
The human safety profile of 5-Amino-1MQ is not well established. The information below is based on theoretical risks, animal data, and anecdotal user reports.
- Common/Minor Side Effects (Anecdotal):
- Increased Thermogenesis: A feeling of being warm or having a slightly elevated body temperature, consistent with an increased metabolic rate.
- Jitteriness or Over-stimulation: Some users report feeling restless or “wired,” similar to a high dose of caffeine, especially when first starting.
- Insomnia: If taken too late in the evening, the stimulating effects can interfere with sleep.
- Injection Site Reactions: For SubQ use, redness, itching, or swelling at the injection site can occur.
- Potential and Theoretical Risks:
- Unknown Long-Term Effects of MNA Suppression: The product of the NNMT reaction, 1-MNA, has anti-thrombotic and anti-inflammatory properties. The consequences of chronically suppressing its production are unknown.
- Impact on Global Methylation: While 5-Amino-1MQ is thought to preserve the SAM methyl pool, the long-term systemic effect on critical epigenetic processes (like DNA methylation) has not been studied in humans.
- Off-Target Effects: As with any pharmacological agent, there is a risk of unintended interactions with other enzymes or receptors, which could lead to unforeseen side effects.
- Lack of Human Data: The most significant risk is the absence of large-scale, long-term human clinical trials. The current understanding of its safety is incomplete.
Stacking and Combinations
- With NAD+ Precursors (NMN or NR): A common protocol involves combining 5-Amino-1MQ with Nicotinamide Mononucleotide (NMN) or Nicotinamide Riboside (NR).
- Rationale: NMN/NR provide the raw material for the NAD+ salvage pathway, while 5-Amino-1MQ prevents that material from being “siphoned off” by NNMT. This creates a powerful synergistic effect to maximize the increase in cellular NAD+.
- Example Protocol: 50-100 mg 5-Amino-1MQ daily + 500-1000 mg NMN or NR daily.
Cycling
Due to the lack of long-term data, a cycling strategy is often employed in research settings to mitigate potential receptor desensitization or unknown side effects.
- Common Cycle: 8-12 weeks “on,” followed by a 4-week “off” period.
Current Status and Regulations
- FDA Approval Status: Not Approved. 5-Amino-1MQ is an investigational compound. It cannot be legally manufactured, marketed, or sold as a dietary supplement or drug for human consumption.
- Legal Availability: It is sold by various chemical supply companies under the label “For Research Use Only” or “Not for Human Consumption.” This places the legal onus on the purchaser. The quality, purity, and concentration of products from these sources are not regulated.
- WADA/USADA Status: Prohibited. 5-Amino-1MQ falls under Category S4. Hormone and Metabolic Modulators on the World Anti-Doping Agency (WADA) Prohibited List. Athletes subject to WADA testing are banned from using it at all times.
- Future Research Directions:
- The next critical step is the initiation of formal, multi-center Phase I and Phase II clinical trials to rigorously evaluate its safety, efficacy, and optimal dosage in human populations for obesity and NAFLD.
- Research is expanding to explore its utility in oncology, particularly for cancers where NNMT is overexpressed.
- Further investigation into its long-term effects on methylation patterns and the consequences of MNA suppression is urgently needed.
The future of 5-Amino-1MQ as a potential therapeutic is promising but hinges entirely on the results of forthcoming human clinical trials. Until then, it remains a powerful but unproven tool for research.