TL;DR
A quinolinium analog of nicotinamide. Mouse fat-loss in one lab. No human trial published.
What is it? A small-molecule NNMT (nicotinamide N-methyltransferase) inhibitor. A quinolinium analog of nicotinamide designed by the Watowich and Neelakantan group at the University of Texas Medical Branch.
What does it do? Blocks NNMT from methylating nicotinamide to 1-methylnicotinamide. Spares NAD+ and SAM pools in white adipose tissue, reduces adipocyte lipogenesis, and raises energy expenditure.
Does the evidence hold up? One lab's program. DIO mice lost body weight, white adipose mass, adipocyte size, and plasma cholesterol without changing food intake (Neelakantan, Biochem Pharmacol 2018, PMID 29155147). Follow-on mouse papers only. No human trial.
Who uses it? Laboratories and a body-composition self-experimenter community. Obtained through compounding pharmacies and research-chemical suppliers. No clinician-supervised indication exists.
Bottom line? A real NNMT target. One lab's mouse work. Zero humans. Gray-market vials are ahead of Phase 1.
What It Is
5-Amino-1MQ (5-amino-1-methylquinolinium) is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT), a cytosolic enzyme that catalyzes the methylation of nicotinamide (vitamin B3 / NAD+ precursor) to 1-methylnicotinamide (1-MNA) using S-adenosylmethionine (SAM) as the methyl donor. It is a quinolinium scaffold — a fused bicyclic aromatic structure carrying a permanent positive charge on the ring nitrogen — that was selected from a structure-activity-relationship (SAR) series developed in the laboratory of Stanley Watowich and Harshini Neelakantan at the University of Texas Medical Branch at Galveston.
NNMT sits at an unusual metabolic intersection. Every molecule of nicotinamide that NNMT methylates is both a NAD+ precursor that has been diverted away from the NAD+ salvage pathway and a methyl group (from SAM) consumed producing a biologically inactive waste product (1-MNA). Over-expressed NNMT therefore drains both the NAD+ pool and the cellular methyl pool at the same time. NNMT expression is markedly elevated in the white adipose tissue (WAT) of diet-induced obese mice and in multiple human metabolic disease states, which is what made the enzyme a target of interest for obesity pharmacology in the first place (Kraus et al., Nature 2014; PMID 24717514).
The Neelakantan / Watowich series screened quinolinium analogs for on-target potency, membrane permeability, and selectivity. 5-Amino-1MQ emerged as the lead compound. It demonstrated inhibition of NNMT in biochemical assay with an IC50 of approximately 1 µM, penetrated adipocytes to reduce intracellular 1-MNA concentrations, raised intracellular NAD+ and SAM, and when administered systemically to diet-induced-obese C57Bl/6J mice reversed the obesity phenotype without altering food intake (Neelakantan et al., J Med Chem 2017; Neelakantan et al., Biochem Pharmacol 2018). This result — fat loss without appetite suppression — is what made 5-Amino-1MQ of interest to the optimization / longevity community.
Practical reality check: everything published on 5-Amino-1MQ comes from the single laboratory group at University of Texas Medical Branch that invented it, and every in vivo result is in mice. There is no human clinical trial, no published human pharmacokinetic data, no independent laboratory replication of the core DIO-mouse result, and no peer-reviewed safety database in any species above rodent. The compound's appearance in compounding pharmacies and research-chemical catalogs in the early 2020s far outpaced the pace of evidence generation. Users should understand that the compound is a credible research tool for NNMT biology with a promising mouse phenotype — not an established human therapy.
Mechanism of Action
5-Amino-1MQ is a substrate-competitive / product-mimetic inhibitor of NNMT. It occupies the nicotinamide-binding pocket of the enzyme and blocks transfer of the methyl group from SAM to nicotinamide. The downstream metabolic consequences stem from the resulting preservation of nicotinamide and SAM pools and the reduction of cellular 1-MNA.
- Direct NNMT enzyme inhibition — Biochemical IC50 around 1 µM against recombinant mouse and human NNMT (Neelakantan et al., J Med Chem 2017; PMID 28493686). Reduces intracellular 1-MNA production in differentiated 3T3-L1 adipocytes at 1–30 µM concentrations without cytotoxicity in the published cell-viability window.
- Intracellular NAD+ preservation — By preventing the methylation loss of nicotinamide from the NAD+ salvage pathway, NNMT inhibition increases the nicotinamide available to NAMPT-mediated NAD+ resynthesis. In NNMT-inhibited adipocytes, intracellular NAD+ rises relative to untreated controls, supporting sirtuin (SIRT1/SIRT3) activity, PARP-dependent DNA repair, and mitochondrial redox balance.
- Intracellular SAM conservation — Each NNMT reaction consumes one SAM molecule. Blocking NNMT preserves SAM for other methylation reactions, including DNA methylation, histone methylation, polyamine synthesis, phosphatidylcholine synthesis, and neurotransmitter production. In the DIO-mouse adipose phenotype, preserved SAM supports epigenetic state and methylation-dependent gene regulation.
- Suppression of adipocyte lipogenesis — In 3T3-L1 and primary mouse adipocytes, 5-Amino-1MQ treatment reduces triglyceride accumulation and adipocyte-marker gene expression, consistent with an anti-lipogenic phenotype rather than a catabolic / lipolytic one (Neelakantan 2018).
- Increased adipocyte energy expenditure — NNMT inhibition shifts adipocyte metabolism toward higher basal oxygen consumption. The phenotype is most consistent with elevated mitochondrial activity driving heat dissipation rather than with direct fatty-acid mobilization.
- Muscle stem cell (satellite cell) niche effects — Separate work on NNMT knockdown has suggested a role in muscle stem cell activation and myogenesis, although this literature is thinner and has not been specifically demonstrated with 5-Amino-1MQ in the same rigor as the adipose phenotype.
- Peripheral-tissue bias — 5-Amino-1MQ is a quaternary ammonium / permanently-charged species; passive blood-brain-barrier penetration is expected to be limited. Published pharmacokinetic characterization (Babula et al., 2024; PMID 39161060) focused on plasma and peripheral tissue distribution in mice after IV, oral, and subcutaneous dosing, and confirmed peripheral-tissue engagement.
- No direct effect on food intake or classical appetite pathways — The DIO-mouse phenotype is explicit: body-weight and adipose-mass reductions occur without changes in food intake or locomotor activity. Mechanism is metabolic, not behavioral.
What the Research Shows
The entire peer-reviewed 5-Amino-1MQ literature is essentially one laboratory's research program plus a small number of citing reviews. The core papers — and the effect sizes they report — are:
- Kraus 2014 (Nature; PMID 24717514) — Demonstrated that NNMT knockdown (antisense oligonucleotide) in white adipose tissue of DIO mice protects against diet-induced obesity. This is the foundational "NNMT as obesity target" paper and the rationale for pharmacologic NNMT inhibition. Does not use 5-Amino-1MQ but frames the target.
- Neelakantan 2017 (J Med Chem; PMID 28493686) — Structure-activity relationship paper for small-molecule NNMT inhibitors. Describes the quinolinium scaffold SAR, identifies 5-Amino-1MQ as membrane-permeable, and demonstrates biochemical and cellular on-target engagement (reduction of intracellular 1-MNA).
- Neelakantan 2018 (Biochem Pharmacol; PMID 29155147) — The pivotal in vivo paper. C57Bl/6J male mice on a high-fat diet received 5-Amino-1MQ systemically for 11 days. Treatment reduced body weight (~7%), decreased white adipose mass (~30%), reduced adipocyte size, and lowered plasma total cholesterol. Food intake was unchanged. Intracellular adipocyte NAD+ and SAM rose; 1-MNA fell. This is the single most-cited 5-Amino-1MQ study and the basis for essentially all downstream interest in the compound.
- Babula 2024 (PMID 39161060) — Characterized plasma pharmacokinetics and tissue distribution of 5A1MQ after single IV (5 mg/kg) and oral (30 mg/kg) dosing and single/multiple subcutaneous dosing (25 mg/kg, once daily for 1 or 5 days) in C57Bl/6J mice. Extended the DIO mouse phenotype to include liver pathology improvements and characterized drug exposure in peripheral tissues. Validated NNMT inhibition as a pharmacologic approach to obesity-related metabolic dysfunction in the mouse.
- Ulanovskaya / Cravatt / Campagna reviews — Multiple review articles frame NNMT as a target in obesity, cancer, fatty-liver disease, aging, and Alzheimer's, often citing the 5-Amino-1MQ SAR series as the pharmacological probe of choice. These are review articles, not independent efficacy replications.
- Muscle / stem-cell line of work — Separate papers (Neff, Dilworth and others) describe NNMT's role in the muscle stem cell niche and the effect of NNMT inhibition on muscle regeneration. This line of work is smaller and less integrated with the 5-Amino-1MQ pharmacology series.
Critical Context — Single Lab, Mouse Only
Essentially every peer-reviewed in vivo 5-Amino-1MQ study is from the Neelakantan / Watowich laboratory at University of Texas Medical Branch at Galveston. There is no independent replication of the DIO-mouse body-composition phenotype from a different laboratory. No human trial has been registered, conducted, or published. Translating mouse effect sizes to humans would require pharmacokinetic bridging (done), toxicology in non-rodent species (not published), a Phase I healthy-volunteer safety study (not registered), and a Phase II efficacy read-out (not initiated). The evidence bar for a research tool compound is different from the evidence bar for a clinical therapy, and 5-Amino-1MQ currently sits on the former side of that line.
Human Data
There is no published human clinical trial of 5-Amino-1MQ. A ClinicalTrials.gov search for "5-amino-1-methylquinolinium," "5-Amino-1MQ," and "5A1MQ" returns no registered human studies as of April 2026.
- No published human pharmacokinetics — All plasma-concentration data is from C57Bl/6J mice (Babula 2024). Whether the mouse subcutaneous or oral exposure translates proportionally to humans has not been established.
- No published human safety database — There is no Phase I healthy-volunteer safety, tolerability, or maximum-tolerated-dose study. The absence of data is not evidence of absence of risk.
- No published human efficacy data for any indication — Not for obesity, not for fatty liver, not for muscle preservation, not for NAD+ biology, not for any clinical endpoint.
- Community use anecdotes — Optimization-community reports describe subjective effects consistent with mild fat-loss, occasional GI upset, and occasional headache. These are uncontrolled self-reports with no placebo comparison and substantial selection bias. They are not equivalent to clinical evidence.
- Compounding pharmacy activity is not evidence — A compounding pharmacy dispensing 5-Amino-1MQ under a prescriber's signature does not constitute human clinical data. Pharmacy dispensing and FDA-recognized evidence are different phenomena.
The practical implication: anyone using 5-Amino-1MQ in a human is conducting an uncontrolled experiment whose safety margin is inferred from mouse data and whose efficacy is a hypothesis. This is an acceptable frame for self-experimentation under clinician supervision with informed consent; it is not acceptable framing for a therapeutic product.
Dosing from the Literature
The following dose information is drawn from the published mouse literature and from community self-experimentation reports. It is not a human dosing recommendation. No FDA-approved dose exists.
| Route / Population | Dose | Frequency | Notes |
|---|
| Mouse IV (PK) | 5 mg/kg | Single dose | Babula 2024 pharmacokinetic reference dose. |
| Mouse oral (PK / efficacy) | 30 mg/kg | Daily | Used in DIO-mouse oral dosing in Babula 2024; efficacy paradigm extended from Neelakantan 2018. |
| Mouse subcutaneous (PK) | 25 mg/kg | Daily × 1–5 days | Babula 2024 SubQ characterization. |
| Community oral (humans) | 50–150 mg | 1–2x daily | Most common optimization-community oral dose; capsule form from compounding pharmacies. No pharmacokinetic or efficacy basis in published human work. |
| Community subcutaneous (humans) | 25–50 mg | Daily | Injectable formulations from some compounding pharmacies. Assumed higher bioavailability than oral but not published. |
| Cycle length (community) | 8–12 weeks | — | With washout periods. No mechanistic basis for this cadence. |
Dosing Disclaimer
No dose-finding study has been conducted in humans. Community doses are anecdotal scale-ups from mouse data. Individual response, off-target effects, and long-term consequences are unstudied. Use only under the supervision of a licensed clinician, with informed consent that you are using an unapproved investigational compound.
Reconstitution & Storage
5-Amino-1MQ is most commonly supplied through compounding pharmacies as oral capsules (anhydrous powder formulation), occasionally as a sublingual troche, and less commonly as a lyophilized powder for subcutaneous reconstitution.
| Presentation | Reconstitution | Typical Concentration | Storage |
|---|
| Oral capsule (most common) | None — pre-filled | 25 / 50 / 100 mg strengths typical | Room temperature, dry, out of light |
| Sublingual troche | None — pre-filled | 25 / 50 mg per troche | Room temperature in sealed container |
| Lyophilized powder (injectable) | Bacteriostatic water | Varies by vendor | Lyophilized: room temp / refrigerated. Reconstituted: 2–8°C, use within 14–28 days |
- Quaternary ammonium chemistry — The permanent positive charge on the ring nitrogen means 5-Amino-1MQ is very water-soluble as a salt. The counter-ion (typically chloride or iodide) depends on the synthesis route.
- Light stability — Quinolinium compounds can be photosensitive. Store lyophilized / powdered material in amber / opaque containers.
- Identity verification — Research-chemical channels should provide HPLC purity and mass-spectrometry confirmation. Independent third-party Certificate of Analysis is the practical floor for confidence.
→ Use the Kalios Dosing Calculator
Side Effects & Risks
Important
5-Amino-1MQ has zero published human trials. Compounding pharmacies supply it outside an approved indication. Ask your provider about NAD/NNMT-pathway strategy before any self-experiment.
The safety profile is essentially inferred from mouse toxicology (which has not been exhaustively published) and from uncontrolled community self-report. The published mouse efficacy studies did not report serious adverse effects at the dose ranges tested, but absence of observed toxicity in an 11-day DIO study is not a full chronic-toxicology package.
- GI discomfort — Mild nausea, stomach discomfort, or altered stool are the most commonly reported subjective effects, particularly with higher oral doses. Taking with food may attenuate.
- Headache — Occasionally reported; possibly related to acute shifts in nicotinamide / SAM dynamics or to off-target CNS effects that have not been systematically studied.
- Methylation dynamics — Long-term alteration of SAM availability could theoretically affect DNA methylation and epigenetic state. The DIO-mouse studies did not track long-term epigenetic consequences; this remains a theoretical concern in chronic human use.
- NNMT has roles beyond adipose — NNMT is expressed in liver (xenobiotic / drug metabolism role), kidney, thyroid, and some CNS regions. Chronic systemic NNMT inhibition could affect drug metabolism (slowed clearance of substrates), thyroid hormone metabolism, and other processes. These have not been studied in humans.
- Cancer interactions — NNMT is upregulated in many tumor types and has been proposed as a tumor-promoting enzyme. The effect of systemic NNMT inhibition on existing occult malignancy is unstudied. This is a theoretical risk, not a demonstrated one, but it warrants age-appropriate cancer screening before chronic use.
- Pregnancy and lactation — No reproductive toxicology data. Do not use.
- Drug interactions — Unstudied. Because NNMT participates in some xenobiotic metabolism pathways, inhibition could theoretically alter the metabolism of medications handled through overlapping enzyme systems.
- No published LD50 in humans — Safety margin is extrapolated from mouse pharmacology, which is not a substitute for species-bridged toxicology.
- Purity risk — Small-molecule research chemicals vary in synthesis quality. Independent mass-spec and HPLC confirmation should be the floor.
- Long-term consequences are unknown — There is no published human study of any duration. Treat chronic use as self-experimentation.
Bloodwork & Monitoring
- Baseline CMP and CBC — Standard pre-use chemistry and complete blood count. Confirm renal and hepatic function.
- Lipid panel — Track total cholesterol, LDL, HDL, triglycerides. In the mouse model, plasma cholesterol decreased; whether the same is observed in humans is uncharacterized.
- HbA1c, fasting glucose, fasting insulin — Track insulin sensitivity and glycemic control. NNMT inhibition improves insulin sensitivity in mice; whether that translates to humans is unstudied.
- Homocysteine and methionine — Reasonable proxies for methylation pathway status. Abrupt changes could suggest methylation-pathway perturbation.
- Liver enzymes (AST, ALT, GGT) — Baseline and periodic. Monitoring is particularly important given hepatic NNMT expression.
- Thyroid panel (TSH, free T4) — Baseline and periodic for long-term use.
- Body composition — DEXA scan or waist-circumference tracking for objective fat-mass change.
- Age-appropriate cancer screening — Before starting chronic use, complete standard screening (colonoscopy, mammography, skin check, PSA, etc., as age-appropriate).
Commonly Stacked With
The most mechanistically logical pairing. 5-Amino-1MQ preserves NAD+ by blocking its nicotinamide loss through NNMT; NAD+ precursors add raw material for NAD+ salvage. The combination attacks the NAD+ pool from both supply and drain. Evidence for the combined intervention in humans does not exist.
GLP-1 / GLP-1+GIP agonists reduce appetite through hypothalamic signaling. 5-Amino-1MQ alters adipocyte energy expenditure without affecting food intake. The two mechanisms are orthogonal. Combination use is reported in community optimization protocols but has no published safety or efficacy data.
Tesamorelin reduces visceral adipose through GH-mediated lipolysis. 5-Amino-1MQ reduces adipocyte mass through energy expenditure. Some advanced body-composition protocols layer the two on different mechanisms. No combined human data exists.
MOTS-c activates AMPK through mitochondrial signaling; 5-Amino-1MQ preserves NAD+ pools that support sirtuin and mitochondrial function. The combined effect on metabolic flexibility is a community hypothesis, not a clinical evidence claim.
→ Check compound compatibility in the Stack Builder
Regulatory Status
Current Status — April 2026
5-Amino-1MQ is not FDA-approved for any indication. It has not entered human clinical trials, and no IND has been publicly disclosed. It is a research compound.
As a small molecule rather than a peptide, 5-Amino-1MQ falls outside the FDA's peptide-specific Bulk Drug Substances Category 1 / Category 2 framework. It is not specifically named on either list. Some 503A compounding pharmacies dispense 5-Amino-1MQ under patient-specific prescriptions invoking the general USP grade bulk powder framework; whether that practice survives scrutiny under current FDA compounding rules is uncertain and has not been directly adjudicated.
5-Amino-1MQ is not specifically listed on the WADA Prohibited List 2026. It could plausibly be evaluated under S4 (Hormone and Metabolic Modulators) if an athletes' agency chose to name it. Athletes subject to anti-doping testing should consult their federation before use.
HHS Secretary Robert F. Kennedy Jr.'s February 2026 peptide-reclassification announcement does not cover 5-Amino-1MQ because the compound is a small molecule and lies outside that framework.
Cost & Access
5-Amino-1MQ is not approved for human use in the United States. It is available through research suppliers for laboratory research purposes only, and some 503A compounding pharmacies dispense it under patient-specific prescriptions.
Availability through compounding pharmacies typically requires a prescription from a licensed provider willing to prescribe an unapproved investigational small molecule. Dosage forms most commonly offered are oral capsules (25, 50, 100 mg) and less commonly sublingual troches or lyophilized powder for subcutaneous reconstitution. Research-chemical channels also sell the powder; identity and purity vary by source.
5-Amino-1MQ is not part of HHS Secretary Robert F. Kennedy Jr.'s February 2026 peptide-reclassification announcement. Its regulatory pathway to broader availability would require a sponsor to pursue an IND / NDA — which no one is publicly doing as of April 2026.
Pricing and availability vary by provider, state, and prescription status. Kalios does not sell compounds.
Related Compounds
People researching 5-Amino-1MQ often also look at these:
Triple monoamine reuptake inhibitor (5-HT, DA, NE). Non-GLP-1 weight-loss alternative.
ERR agonist (estrogen-related receptor). Exercise-mimetic small molecule.
AMPK activator (AICA ribonucleotide). Exercise-mimetic small molecule with WADA ban history.
Key References
- Neelakantan H, Brightwell CR, Graber TG, Maroto R, Wang HL, McHardy SF, Papaconstantinou J, Fry CS, Watowich SJ. 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. PMID: 30885768.
- Neelakantan H, Wang HY, Vance V, Hommel JD, McHardy SF, Watowich SJ. Structure-Activity Relationship for Small Molecule Inhibitors of Nicotinamide N-Methyltransferase. J Med Chem. 2017;60(12):5015-5028. PMID: 28493686.
- Neelakantan H, Vance V, Wetzel MD, Wang HL, McHardy SF, Finnerty CC, Hommel JD, Watowich SJ. 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. PMID: 29155147. (The pivotal in vivo DIO-mouse paper.)
- Babula JJ, Bui D, Stevenson HL, Watowich SJ, Neelakantan H. Nicotinamide N-methyltransferase inhibition mitigates obesity-related metabolic dysfunction. Diabetes Obes Metab. 2024. PMID: 39161060. (Pharmacokinetic characterization of 5A1MQ after IV, oral, and SubQ dosing in DIO mice, plus extension of the efficacy phenotype.)
- Kraus D, Yang Q, Kong D, Banks AS, Zhang L, Rodgers JT, Pirinen E, Pulinilkunnil TC, Gong F, Wang YC, Cen Y, Sauve AA, Asara JM, Peroni OD, Monia BP, Bhanot S, Alhonen L, Puigserver P, Kahn BB. Nicotinamide N-methyltransferase knockdown protects against diet-induced obesity. Nature. 2014;508(7495):258-262. PMID: 24717514. (Foundational target-validation paper.)
- Pissios P. Nicotinamide N-Methyltransferase: More Than a Vitamin B3 Clearance Enzyme. Trends Endocrinol Metab. 2017;28(5):340-353. PMID: 28291578.
- Campagna R, Pozzi V, Sartini D, Salvolini E, Brisigotti V, Molinelli E, Campanati A, Offidani A, Emanuelli M. Beyond Nicotinamide Metabolism: Potential Role of Nicotinamide N-Methyltransferase as a Biomarker in Skin Cancers. Cancers (Basel). 2021;13(19):4943. PMID: 34638428.
- Liu Y, Gong W, Yang ZY, Zhou XS, Gong C, Zhang TR, Wei X, Ma D, Ye F, Gao QL. Quercetin induces protective autophagy and apoptosis through ER stress via the p-STAT3/Bcl-2 axis in ovarian cancer. Apoptosis. 2017;22(4):544-557. (Contextual NNMT-adjacent biology.)
- Roberti A, Fernández AF, Fraga MF. Nicotinamide N-methyltransferase: At the crossroads between cellular metabolism and epigenetic regulation. Mol Metab. 2021;45:101165. PMID: 33453418.
- Ulanovskaya OA, Zuhl AM, Cravatt BF. NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink. Nat Chem Biol. 2013;9(5):300-306. PMID: 23455543.
- Komatsu M, Kanda T, Urai H, Kurokochi A, Kitahama R, Shigaki S, Ono T, Yukioka H, Hasegawa K, Tokuyama H, Kawabe H, Wakino S, Itoh H. NNMT activation can contribute to the development of fatty liver disease by modulating the NAD+ metabolism. Sci Rep. 2018;8(1):8637. PMID: 29872148.
- Hong S, Moreno-Navarrete JM, Wei X, Kikukawa Y, Tzameli I, Prasad D, Lee Y, Asara JM, Fernandez-Real JM, Maratos-Flier E, Pissios P. Nicotinamide N-methyltransferase regulates hepatic nutrient metabolism through Sirt1 protein stabilization. Nat Med. 2015;21(8):887-894. PMID: 26168293.
- Brightwell CR, Latham CM, Thomas NT, Keeble AR, Murach KA, Fry CS. A glitch in the matrix: the pivotal role for extracellular matrix remodeling during muscle hypertrophy. Am J Physiol Cell Physiol. 2022;323(3):C763-C771. PMID: 35876283. (Satellite-cell / NNMT context.)
Last updated: April 2026 | Profile authored by Kalios Peptides research team