5-Amino-1MQ

5-Amino-1MQ (5-amino-1-methylquinolinium, also called 5-AMQ) is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), the enzyme that attaches a methyl group to nicotinamide, a form of vitamin B3 ¹. That reaction consumes S-adenosylmethionine (SAM), the body's main methyl donor, and pulls nicotinamide away from the pathway that rebuilds NAD+, a central coenzyme in energy metabolism. When NNMT runs high, as it appears to do in the fat tissue of obesity and the skeletal muscle of aging, blocking it raises intracellular NAD+ and SAM and reduces fat synthesis ¹.

The compound emerged from a search for selective NNMT inhibitors led by researchers at UTMB, who reported anti-obesity effects in diet-induced obese mice ¹ and then showed improved muscle stem cell function in aged mice ². Later work by that group described the combination with a reduced-calorie diet ³, microbiome shifts ⁴, exercise-additive effects ⁵, and rat pharmacokinetics ⁶. Independent laboratories have also examined NNMT inhibition in cancer cell lines and kidney disease models ⁸.

All efficacy evidence is preclinical today. There are no published human trials, so claims about human effects remain extrapolations from animal and cell data ¹.

5-Amino-1MQ reduces NNMT activity rather than removing the enzyme. The molecule is a methylquinolinium compound with a primary amine substitution that allows it to cross cell membranes by passive and active transport ¹. Once inside, 5-Amino-1MQ acts as a direct, competitive, membrane-permeable NNMT inhibitor that lowers 1-MNA and raises NAD+ and SAM in cells ¹. A turnover-inhibitor mechanism, in which NNMT methylates the inhibitor and the resulting charged product potently inhibits the same enzyme, has been demonstrated only for nicotinamide-analog NNMT inhibitors such as the 6-MeO-NA class, not for 5-Amino-1MQ itself ⁷.

Inside fat cells, NNMT inhibition lowers 1-methylnicotinamide (1-MNA), raises NAD+ and SAM, and suppresses lipogenesis, the process by which fat cells store lipid ¹. In aged muscle, where NNMT overexpression is linked to impaired NAD+ salvage and reduced sirtuin 1 (SIRT1) activity, inhibition restored muscle stem cell proliferation and fusion in mice ².

Key downstream findings:

• Fat and liver: In diet-induced obese mice, NNMT inhibition combined with a reduced-calorie diet normalized body composition, liver weight, and hepatic steatosis ³.
• Muscle: In aged mice, the inhibitor alone raised grip strength about 40% versus sedentary controls, and combined with exercise the gain reached about 60% ⁵.
• Tumor stroma: In cancer-associated fibroblasts, NNMT depletes SAM and rewires histone methylation, which supports tumor progression ¹⁰.
• Kidney: NNMT inhibition reduced tubular senescence and fibrosis in early chronic kidney disease models ¹².

The strongest quantitative data come from aging-muscle studies and diet-induced obese mice ¹. No human efficacy studies exist.

• Body composition: In diet-induced obese mice, NNMT inhibitor treatment reduced body weight, white adipose mass, adipocyte size, and plasma total cholesterol without changing total food intake or causing observable adverse effects ¹. Combined with a reduced-calorie diet switch, it normalized body composition, liver weight, epididymal white adipose weight, and hepatic steatosis to lean-control levels, where the diet switch alone did not ³.
• Muscle function: In 24-month-old mice given 5-10 mg/kg for 1-3 weeks after injury, treatment increased muscle stem cell proliferation and fusion, produced about 2-fold greater myofiber cross-sectional area, and raised peak torque by about 70% ². In sedentary aged mice, NNMT inhibition alone produced about 40% greater grip strength, exercise alone produced about 20%, and the combination produced about 60% ⁵.
• Cancer cell lines: NNMT inhibitors including 5-AMQ (together with 6MeONa and EL-1) reduced viability, increased reactive oxygen species, and triggered apoptosis in osteosarcoma and Merkel cell carcinoma lines, and enhanced cisplatin sensitivity ⁸. The related NNMT inhibitor 5-methylquinolinium (5MQ) inhibited HeLa cervical cancer cell proliferation in a concentration- and time-dependent manner while sparing HEK-293 cells ⁹. In a bladder cancer mouse model, it reduced tumor growth and enhanced anti-PD-L1 activity ¹¹.
• Kidney: Selective NNMT inhibition reduced tubular senescence and fibrosis in kidney organoids and in vivo ¹².

All efficacy protocols are mouse or in vitro, and no validated human dose exists ². Community protocols fill the gap, calibrated against rat pharmacokinetics and allometrically scaled mouse doses ⁶.

Published animal anchors:

• Aged-muscle regeneration: 5 or 10 mg/kg systemically for 1 or 3 weeks after injury ².
• Aging muscle with or without exercise: daily dosing across 8 weeks in 22-24-month-old mice ⁵.
• Diet-induced obesity: multi-week NNMT inhibition combined with a low-fat diet switch ³.

Community oral protocols commonly use 50-150 mg/day, split 25-50 mg two to three times daily for 4-8 weeks; some protocols reach about 200 mg/day. Parenteral community protocols use 50-150 mg/day total subcutaneously, typically around 1 mg/kg, split 25-50 mg two to three times daily for 6-10 weeks. Protocol writers generally prefer divided dosing because the rat half-life is short ⁶.

Allometric conversion maps mouse 5-10 mg/kg doses to roughly 0.41-0.81 mg/kg in humans, or about 30-65 mg/day for a 75-80 kg adult ². Community practice typically runs higher at 1-2 mg/kg, and no human pharmacokinetic or safety data validate that gap ⁶.

5-Amino-1MQ is supplied as the iodide salt of a quaternary ammonium cation (5-amino-1-methylquinolinium), not as a peptide ¹. Salt-form note: the iodide salt is about 286 g/mol and the iodide counterion contributes roughly 44% of the mass, so doses expressed as the cation versus the iodide salt differ about 1.8-fold; community dose numbers should state which form they refer to (community protocol). Purchasing note: products sold as '5MQ' are sometimes plain 5-methylquinolinium rather than 5-amino-1-methylquinolinium, and the literature itself uses the shorthand inconsistently ⁹, so verify the full chemical name and CAS number before ordering. Because it is a water-soluble small molecule with no peptide aggregation or denaturation concerns, reconstitution in an aqueous diluent is straightforward ¹.

Bacteriostatic water (0.9% benzyl alcohol) is standard for multi-dose vials; sterile water for injection or 0.9% saline is used for single-dose preparations. Add the diluent slowly, agitate gently, and allow roughly 10 minutes for full dissolution. The research literature notes filtering through a 0.22 µm syringe filter before injection (community protocol).

For storage, keep the dry powder in a sealed, desiccated, light-protected vial at −20°C for long-term storage; 2-8°C is acceptable for short-term use up to 30 days (community protocol). Once reconstituted, refrigerate at 2-8°C and protect from light. Community guidance is to use bacteriostatic-water preparations within about 30 days and sterile-water preparations within 24 hours at room temperature. Avoid repeated freeze-thaw cycles because salt precipitation can occur at low temperature (community protocol).

5-Amino-1MQ is stable in plasma under standard storage and handling conditions, with less than 15% variation in a validated assay ⁶. No published human stability or shelf-life data exist.

No controlled human drug-interaction studies exist for 5-Amino-1MQ. The notes below extrapolate from rat pharmacokinetics and mouse efficacy studies ⁶.

• Nicotinamide and NAD+ precursors: Nicotinamide is the NNMT substrate, so high-dose nicotinamide or niacin could theoretically compete with 5-Amino-1MQ and blunt efficacy (mechanistic extrapolation; no specific threshold established); ordinary multivitamin levels are unlikely to interfere ⁷. NMN and nicotinamide riboside may be redundant because NNMT inhibition already raises NAD+ ¹.
• Methylation-related drugs: NNMT inhibition raises SAM and spares the methyl-donor pool, so agents metabolized by methylation, such as azathioprine and levodopa, and methotrexate, whose action depends on folate pathways, could theoretically be affected ¹.
• Chemotherapy: In osteosarcoma and Merkel cell carcinoma lines, NNMT inhibitors including 5-Amino-1MQ (together with 6MeONa and EL-1) increased reactive oxygen species and apoptosis and enhanced cisplatin sensitivity ⁸. That is in vitro evidence only and not a basis for an unsupervised combination.
• Immune checkpoint inhibitors: In a bladder cancer mouse model, 5-amino-1-methylquinolinium iodide reduced tumor growth and enhanced anti-PD-L1 activity ¹¹. Human relevance is unknown.
• GLP-1 receptor agonists: Mouse NNMT inhibition plus calorie reduction normalized body composition where diet alone did not ³, and community protocols often pair 5-Amino-1MQ with semaglutide or tirzepatide for metabolic goals. Monitor for excessive weight loss if combining.
• Metformin and renal cation transport: 5-Amino-1MQ is renally cleared and carries a positive charge ⁶, so theoretical competition at renal cation transporters could alter metformin exposure.

No tolerance or desensitization has been documented in the available research. Cycling is driven by the limited duration of animal exposure and methylation considerations rather than a measured loss of effect ¹.

The longest continuous published dosing window with safety observations is 8 weeks in aged mice, with no food-intake changes or adverse events noted ⁵. Community cycles therefore tend to keep human exposure in or near this window. Common oral cycles include:

• Fat loss: 100-150 mg/day split twice daily for 4-8 weeks, followed by 4 weeks off.
• Metabolic health: 50-75 mg/day split twice daily for 4-8 weeks, followed by 4-6 weeks off.
• Muscle recomp: 100-150 mg/day plus resistance training for 4-8 weeks, followed by 4 weeks off.

Some protocols reach about 200 mg/day (community protocol). Subcutaneous community cycles typically run 50-150 mg/day total, split two to three times daily, for 6-8 weeks (community protocol).

The rationale for off-periods has two parts. First, the turnover-inhibitor mechanism, in which methylated inhibitor product builds up at the enzyme, is specific to nicotinamide-analog NNMT inhibitors that NNMT methylates ⁷ and does not apply to directly inhibiting 5-Amino-1MQ, so off-periods for 5-Amino-1MQ rest instead on the limited animal exposure window ⁵. Second, NNMT inhibition raises SAM, the body's principal methyl donor, so periodic washout lets methylation flux re-equilibrate between cycles ¹. Mouse data also suggest benefits plateau once body composition normalizes, which supports endpoint-based cycling ³.

Community practice describes several signals for an early cycle exit: a 2-3 week plateau, persistent gut changes, a rebound in 1-MNA despite dosing, or late-cycle fatigue. A 12-week calendar cap is common because no published animal course exceeds 8 weeks ⁵.

Community protocols often sequence or stack 5-Amino-1MQ with metabolic and recovery agents. The mouse data support training and dietary deficit as core co-interventions ³.

• Exercise: This is the best-validated combination. Aged mice gained about 40% grip strength with NNMT inhibition alone, about 20% with exercise alone, and about 60% when combined ⁵.
• GLP-1 receptor agonists: In mouse studies, NNMT inhibition plus a calorie-reduced diet normalized body composition to lean-control levels where diet alone did not ³. Semaglutide and tirzepatide are common community pairings because the appetite-driven deficit from a GLP-1 agonist complements the metabolic shift from NNMT inhibition. No human combination data exist.
• Growth hormone secretagogues: CJC-1295 with ipamorelin, or tesamorelin, act on the GH/IGF-1 axis rather than NAD+/SAM. Community recomp stacks pair them with 5-Amino-1MQ on the assumption that the axes are complementary.
• Recovery peptides: BPC-157 and TB-500 appear in injury-recovery stacks because NNMT inhibition increased muscle stem cell proliferation and post-injury peak torque in aged mice ².
• Avoid stacking multiple NNMT inhibitors: Combining 5-Amino-1MQ with compounds such as 5MQ or 6-MeO-NA class NNMT inhibitors would be redundant and unstudied.

5-Amino-1MQ is a research-only compound with no FDA approval, no publicly recorded IND, and no published human trial; the evidence base remains mouse, rat, and cell-line work ¹.

Regulatory profile:

• Not scheduled under the Controlled Substances Act.
• Not considered a dietary ingredient under U.S. law, so it cannot lawfully be sold as a supplement ingredient. Distribution occurs through research-chemical channels labeled not for human consumption.
• Not an FDA-approved bulk drug substance for pharmacy compounding.
• No marketing authorization in the EU, UK, Australia, Canada, Japan, or China.

For sports, 5-Amino-1MQ is not listed on the WADA Prohibited List in the current evidence base. WADA S0 can apply in principle to substances without human therapeutic approval, but no enumerated S0 listing for 5-Amino-1MQ is documented here, and no athlete sanctions appear in the reviewed material. The performance rationale rests on preclinical muscle data, not on human evidence ².

All safety evidence is preclinical. In anti-obesity and aged-muscle mouse studies, NNMT inhibitor dosing produced no food-intake changes and no observable adverse effects over multi-week courses ¹.

• Animal observations: No adverse events were reported in the rat pharmacokinetic study ⁶.
• Community-reported effects: Transient mild nausea or gastrointestinal upset is the most common early complaint at typical oral doses and often settles when taken with food. Mild headache or fatigue can occur in the first week, and occasional sleep disruption is reported above 150 mg/day. No sedation, appetite suppression, or cardiovascular symptoms are reported (community protocol).
• Cancer-line selectivity: In studies of the related inhibitor 5-methylquinolinium (5MQ), HEK-293 cells were spared at concentrations that inhibited HeLa cells ⁹, but that in vitro selectivity has not been demonstrated across human tissues.
• Key unknowns: No human safety or pharmacokinetic data exist. Long-term SAM and NAD+ elevation could affect methylation in normal tissues ¹. 1-MNA has independent bioactivities, and the consequences of chronically suppressing it are unstudied ¹.
• Working cautions: Pregnancy and breastfeeding are treated as absolute cautions because no developmental data exist. Relative cautions include severe renal impairment because the compound is renally cleared ⁶, active malignancy on immunotherapy, concurrent chemotherapy, and high-dose nicotinamide.

Monitoring discussed in community practice includes creatinine/eGFR, ALT/AST, fasting glucose, HbA1c, lipids, and 1-MNA as a target-engagement marker.