5-Amino-1MQ (5-amino-1-methylquinolinium) is a small experimental molecule that blocks an enzyme called nicotinamide N-methyltransferase (NNMT). A research group at the University of Texas Medical Branch developed it in 2017 as a tool compound and possible drug lead for obesity and age-related muscle loss. It is not a steroid, a SARM or a peptide.
The single most important fact is that no human trial of 5-amino-1MQ has been published or registered. Everything known about its effects comes from cell culture, mice and rats, and almost all of it comes from one research group and the company its founder started.
This page summarizes what the published laboratory and animal studies report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Class | Small-molecule NNMT inhibitor (methylquinolinium) |
| Development stage | Preclinical; no human trials found on ClinicalTrials.gov |
| Formula / weight | C₁₀H₁₁N₂⁺ (a permanently charged cation), 159.2 g/mol |
| Potency | IC50 ≈ 1.2 µM against NNMT in a biochemical assay |
| Routes studied | Subcutaneous injection in mice; IV and oral in rats and mice |
| Half-life | No human data. 3.8 h (IV) and 6.9 h (oral) in rats; 6.3–14.8 h in mice depending on route |
| Oral bioavailability | 38.4% in rats; 3.5% in mice |
| US status | Not an approved drug; not a scheduled controlled substance |
| WADA status | Not named; falls under S0 (non-approved substances) |
What it is
NNMT is an enzyme active in tissues including fat, liver and skeletal muscle. It attaches a methyl group to nicotinamide (a form of vitamin B3), using S-adenosylmethionine (SAM, the body’s main methyl donor), and produces 1-methylnicotinamide (1-MNA). Nicotinamide is a building block of NAD+, a coenzyme central to energy metabolism, so higher NNMT activity diverts nicotinamide away from NAD+ recycling (Kraus et al., Nature 2014; Babula et al., DOM 2024).
This makes 5-amino-1MQ different from NAD+ itself and from NAD+ precursors such as NMN and NR: it supplies nothing, but blocks an enzyme that consumes nicotinamide. See also NAD+.
The interest in blocking NNMT comes from three lines of evidence:
- Mouse genetics. Knocking down NNMT in the fat and liver of mice protected them against diet-induced obesity, raised energy expenditure, and increased SAM and NAD+ in fat tissue (Kraus et al., Nature 2014).
- Human fat tissue. People with type 2 diabetes had about twice the NNMT expression in their fat tissue as controls. Expression tracked insulin resistance and fell after exercise or bariatric surgery (Kannt et al., Diabetologia 2015).
- Population data. In 1,160 Chinese adults, higher blood 1-MNA was associated with higher odds of overweight/obesity and diabetes (Liu et al., JCEM 2015).
These are associations and animal knockouts, not proof that blocking the enzyme helps people. The mouse genetics are also less uniform than often presented. In a second group’s study, mice lacking NNMT entirely had better insulin sensitivity on a high-fat diet, but no better glucose tolerance, and results differed by sex and diet (Brachs et al., Diabetes 2019).
5-Amino-1MQ came out of a structure-activity study that screened methylated quinolinium and related compounds. Quinoliniums gave the best NNMT inhibition, with IC50 values (the concentration that halves enzyme activity) around 1 µM (Neelakantan et al., J Med Chem 2017). PubChem lists the molecule as 1-methylquinolin-1-ium-5-amine, CID 950107 (PubChem).
The 2018 follow-up chose 5-amino-1MQ as the lead compound because it combined potency with good cell permeability (Neelakantan et al., Biochem Pharmacol 2018):
| Compound | NNMT IC50 | Membrane permeability (PAMPA) |
|---|---|---|
| 1-Methylquinolinium (parent) | 12.1 µM | None |
| 1,8-diMQ | 1.8 µM | Low |
| 7-amino-1MQ | 2.6 µM | High |
| 5-amino-1MQ | 1.2 µM | High |
In the same paper, 5-amino-1MQ:
- did not meaningfully inhibit related methyltransferases (DNMT1, PRMT3, COMT) or the NAD+ salvage enzymes NAMPT and SIRT1 at the concentrations tested;
- lowered 1-MNA inside cultured fat cells (EC50 2.3 µM);
- raised NAD+ about 1.2–1.6-fold and raised SAM in cultured fat cells;
- cut fat accumulation in differentiating fat cells by 50% at 30 µM and 70% at 60 µM.
All of these are cell-culture results.
Pharmacokinetics (animal data only)
There is no human pharmacokinetic study. Two animal studies give quite different pictures of oral absorption.
| Species and route | Dose | Half-life | Other findings | Source |
|---|---|---|---|---|
| Rat, IV | Not stated in abstract | 3.8 h | — | Awosemo et al. 2021 |
| Rat, oral | Not stated in abstract | 6.9 h | Peak 2,252 ng/mL; bioavailability 38.4% | Awosemo et al. 2021 |
| Mouse, IV | 5 mg/kg | 6.3 h | High clearance; large volume of distribution | Babula et al. 2024 |
| Mouse, subcutaneous | 25 mg/kg, single or 5 daily doses | 13.3 h / 12.8 h | Peak 7,010 ng/mL at ≈15 min | Babula et al. 2024 |
| Mouse, oral | 30 mg/kg | 14.8 h | Peak only 14.5 ng/mL at 4 h; bioavailability 3.5% | Babula et al. 2024 |
The mouse authors attributed the poor oral exposure to limited gut absorption and heavy first-pass metabolism in the liver. In mouse liver cells the compound’s half-life was under 7 minutes. Even after subcutaneous injection, plasma levels stayed above the mouse NNMT IC50 (78 ng/mL) for only about 2–4 hours. The drug did build up in fat and muscle, where tissue-to-plasma ratios rose to 31 and 17 by 8 hours (Babula et al., DOM 2024).
How either result translates to people is unknown. Every efficacy study in animals used injection, not oral dosing.
Regulatory status
- Approval. 5-Amino-1MQ is not approved as a medicine by the FDA or, as far as we could find, any other regulator. A search of ClinicalTrials.gov for “5-amino-1MQ” and “5-amino-1-methylquinolinium” returned no registered studies (ClinicalTrials.gov).
- Controlled substances. It is not named in the US Schedule III list, which covers the anabolic steroids (21 CFR 1308.13).
- Sport. The WADA list does not name 5-amino-1MQ or NNMT inhibitors. Its S0 class prohibits at all times any pharmacological substance not covered elsewhere on the list that has no current approval for human therapeutic use, including drugs in preclinical development (WADA 2026 Prohibited List). 5-Amino-1MQ fits that description.
What the research shows
All studies below were in mice, gave the drug by injection, and were run by the developer’s group. From 2021 onward the papers declare that the senior author founded Ridgeline Therapeutics, which develops NNMT inhibitors, and that co-authors were employees.
Obesity in mice
First test (2018). Diet-induced obese mice (n = 9 per group) received 5-amino-1MQ, 20 mg/kg by injection three times a day (≈34 mg/kg/day), or saline for 11 days (Neelakantan et al., Biochem Pharmacol 2018):
| Measure | Saline | 5-Amino-1MQ |
|---|---|---|
| Body weight change | +0.6 g (≈ +1.4%) | −2.0 g (≈ −5.1%) |
| Cumulative food intake | 28.1 g | 26.2 g (not different) |
| Epididymal fat pad mass | — | ≈35% lower |
| Fat cell size | — | Over 30% smaller |
| Total cholesterol | — | ≈30% lower |
Dose comparison (2024). Diet-induced obese mice (n = 8 per group) got saline, 10 mg/kg/day or 32 mg/kg/day once daily for 30 days while staying on the high-fat diet (Babula et al., DOM 2024):
| Measure | Saline | 10 mg/kg/day | 32 mg/kg/day |
|---|---|---|---|
| Weight gain over study | 5.4 g | 5.2 g | 0.9 g |
| Fat mass gain | 4.7 g | 4.7 g | 1.3 g |
| Fed-state insulin, day 0 to day 28 | +112% | +46% | −9% |
| Lean mass | No significant treatment effect | — | — |
Only the higher dose limited weight and fat gain. Food intake did not differ. The higher dose also improved glucose tolerance, lowered liver weight (1.4 g vs 2.1 g), reduced microvesicular fatty liver by 73%, and lowered the liver enzymes ALT and AST. In other words, the drug slowed weight gain in mice that kept eating a high-fat diet; it did not cause weight loss in this study.
With a diet change (2021). Obese mice were switched to a lower-fat diet and given either 5-amino-1MQ or saline daily for about 7 weeks (Sampson et al., Sci Rep 2021). Groups had 6–8 mice.
| Measure | Diet switch + saline | Diet switch + 5-amino-1MQ |
|---|---|---|
| Body weight change at study end | −2.9 g (partial regain after day 20) | −6.3 g |
| Fat mass loss from baseline | ≈2.9% | ≈29.3% |
| Lean mass as share of body weight | Unchanged | +6.4% |
The treated mice ended near the body weight and fat mass of mice that had always eaten the lean diet. A companion analysis of the same experiment reported a distinct gut microbiome pattern in the treated mice (Dimet-Wiley et al., Sci Rep 2022).
Aged muscle in mice
Injury recovery (2019). Aged mice (24 months old) had a chemical injury to one lower-leg muscle. They received saline or 5-amino-1MQ at 5 or 10 mg/kg by injection twice daily (Neelakantan et al., Biochem Pharmacol 2019). In treated mice:
- muscle stem cells proliferated and fused into damaged fibers more;
- regenerating fibers had nearly twice the cross-sectional area;
- peak torque of the injured muscle was about 70% higher than in controls.
Exercise in aged mice (2024). Thirty-five female mice aged 22 months received saline or 10 mg/kg/day for 8 weeks, with or without weighted wheel running (Dimet-Wiley et al., Sci Rep 2024):
| Group | Grip strength vs sedentary controls |
|---|---|
| Exercise alone | ≈ +20% |
| 5-Amino-1MQ alone (sedentary) | ≈ +40% |
| 5-Amino-1MQ + exercise | ≈ +60% |
The combination also increased the size of fibers in the calf muscle. The authors note that mice assigned to the drug started about 10% heavier than their controls, because randomization was by cage.
These results concern aged and injured mouse muscle. We found no study testing 5-amino-1MQ for muscle growth in young, healthy animals or in people, and the 2024 obesity study found no effect on lean mass.
Side effects and risks
No human safety data
Because no human has been studied, there is no information on side effects, safe exposure, drug interactions, or effects in pregnancy, liver disease or kidney disease. The animal papers report that treatment was well tolerated, but they were short (11 days to 8 weeks), small, and not designed as toxicology studies. In the 2018 study, a two-mouse dose-escalation run found 60 mg/kg/day “well tolerated with no observable adverse effects” (Neelakantan et al., Biochem Pharmacol 2018). That is not a formal safety assessment.
Signals worth noting from the animal and lab work
- MAO-A inhibition. In an off-target screening panel at 10 µM, 5-amino-1MQ inhibited monoamine oxidase A (MAO-A, an enzyme that breaks down serotonin, norepinephrine and dietary tyramine) by 67.4%. It showed no significant activity at the other receptors and enzymes tested (Babula et al., DOM 2024). Whether this matters at real-world exposures is unknown, since no human data exist.
- White blood cells. The higher dose lowered total white blood cell counts in obese mice, with lymphocytes down 31% and monocytes down 50% compared with controls (Babula et al., DOM 2024). The authors grouped this with other “improved” blood measures; its meaning has not been studied further.
- Methyl and NAD+ balance. The mechanism shifts SAM and NAD+ levels in tissues. The long-term consequences of chronically blocking a methylation enzyme in people have not been studied.
Product quality
5-Amino-1MQ is not an approved drug, so no product sold under this name is made to pharmaceutical standards for identity, purity or dose. We found no published laboratory analysis of commercial products. The animal data also suggest that oral absorption may be poor, at least in mice.
Key takeaways
- An NNMT enzyme blocker, not a hormone. It inhibits nicotinamide N-methyltransferase (IC50 ≈ 1.2 µM), which in cell culture raised NAD+ and SAM in fat cells.
- Animal data only. No human trial has been published or registered. Every efficacy result comes from mice given injections.
- Effects in mice were real but specific. At about 32–34 mg/kg/day it reduced weight or limited weight and fat gain in obese mice without changing food intake, and it improved aged-muscle regeneration and grip strength.
- Oral use is unproven. Oral bioavailability was 38% in rats but only 3.5% in mice, and we found no published study of oral dosing for any efficacy outcome.
- One research group. Nearly all 5-amino-1MQ studies come from the developer’s group, which declares ties to a company developing NNMT inhibitors.
- Unknown human safety. Lab and mouse signals include MAO-A inhibition and lower white cell counts; their relevance to people is unknown.
Sources
- Neelakantan H, Wang HY, Vance V, et al. Structure-activity relationship for small molecule inhibitors of nicotinamide N-methyltransferase. J Med Chem. 2017;60(12):5015–5028. PubMed.
- Neelakantan H, Vance V, Wetzel MD, et al. Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice. Biochem Pharmacol. 2018;147:141–152. PubMed.
- Awosemo O, Neelakantan H, Watowich S, et al. Development & validation of LC-MS/MS assay for 5-amino-1-methyl quinolinium in rat plasma: application to pharmacokinetic and oral bioavailability studies. J Pharm Biomed Anal. 2021;204:114255. PubMed.
- Babula JJ, Bui D, Stevenson HL, Watowich SJ, Neelakantan H. Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Diabetes Obes Metab. 2024;26(11):5272–5282. PubMed.
- Sampson CM, Dimet AL, Neelakantan H, et al. Combined nicotinamide N-methyltransferase inhibition and reduced-calorie diet normalizes body composition and enhances metabolic benefits in obese mice. Sci Rep. 2021;11(1):5637. PubMed.
- Dimet-Wiley A, Wu Q, Wiley JT, et al. Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice. Sci Rep. 2022;12(1):484. PubMed.
- Neelakantan H, Brightwell CR, Graber TG, et al. Small molecule nicotinamide N-methyltransferase inhibitor activates senescent muscle stem cells and improves regenerative capacity of aged skeletal muscle. Biochem Pharmacol. 2019;163:481–492. PubMed.
- Dimet-Wiley AL, Latham CM, Brightwell CR, et al. Nicotinamide N-methyltransferase inhibition mimics and boosts exercise-mediated improvements in muscle function in aged mice. Sci Rep. 2024;14(1):15554. PubMed.
- Kraus D, Yang Q, Kong D, et al. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258–262. PubMed.
- Kannt A, Pfenninger A, Teichert L, et al. Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance. Diabetologia. 2015;58(4):799–808. PubMed.
- Liu M, Li L, Chu J, et al. Serum N(1)-methylnicotinamide is associated with obesity and diabetes in Chinese. J Clin Endocrinol Metab. 2015;100(8):3112–3117. PubMed.
- Brachs S, Polack J, Brachs M, et al. Genetic nicotinamide N-methyltransferase (Nnmt) deficiency in male mice improves insulin sensitivity in diet-induced obesity but does not affect glucose tolerance. Diabetes. 2019;68(3):527–542. PubMed.
- National Center for Biotechnology Information. 1-Methylquinolin-1-ium-5-amine, PubChem CID 950107. PubChem.
- ClinicalTrials.gov. Search for 5-amino-1-methylquinolinium (no registered studies as of October 2026). ClinicalTrials.gov.
- World Anti-Doping Agency. The 2026 Prohibited List, section S0 (non-approved substances). WADA 2026 Prohibited List.
- Code of Federal Regulations. 21 CFR 1308.13, Schedule III. 21 CFR 1308.13.