5-amino-1MQ

5-amino-1-methylquinolinium

Rank#999
Weight LossNot ApprovedAnimalResearchOral

Popular for:Fat loss, metabolic health, NNMT inhibition

0

Total Studies

0

Human Studies

Animal

Evidence Level

Not Approved

FDA Status

Overview

5-amino-1MQ (5-amino-1-methylquinolinium) is a small molecule inhibitor of nicotinamide N-methyltransferase (NNMT), an enzyme increasingly recognized as a key regulator of cellular metabolism and adipogenesis. It is not a peptide but a quinolinium-based compound that has gained significant attention in the biohacking and weight management communities for its potential as a non-stimulant fat loss agent.

**Mechanism of Action: **5-amino-1MQ is a selective, membrane-permeable inhibitor of NNMT. NNMT catalyzes the methylation of nicotinamide (vitamin B3/NAM), consuming SAM (S-adenosyl methionine) as a methyl donor. By inhibiting NNMT, 5-amino-1MQ: (1) Increases intracellular NAD+ levels (boosting cellular energy metabolism), (2) Increases SAM availability (the universal methyl donor), (3) Reduces adipocyte size and white adipose tissue mass, (4) Promotes energy expenditure without affecting food intake. NNMT is overexpressed in adipose tissue of obese individuals, making it a rational therapeutic target.

Mechanism of Action

- Potent, cell-permeable NNMT inhibitor (IC₅₀ around ~1.2 µM in primary reports). In adipocytes, NNMT inhibition increases intracellular NAD⁺ and SAM pools and shifts metabolism/energy expenditure. PubMed+1

- NNMT is elevated in adipose and liver with obesity; genetic knockdown in mice protects against diet-induced obesity by boosting energy expenditure and altering polyamine flux. Foundational target-biology paper. PMC

Key Research Benefits

Fat loss without appetite suppression: In diet-induced obese mice, 5-amino-1MQ reduced body weight, white adipose mass, and adipocyte size without impacting food intake (Neelakantan et al., 2018, Biochem Pharmacol, PMC 5826726).
NAD+ restoration: NNMT inhibition increases intracellular NAD+ levels, boosting mitochondrial function, cellular energy, and potentially activating sirtuins (longevity-associated proteins).
Increased SAM availability: By reducing SAM consumption by NNMT, more SAM is available for DNA/histone methylation and other critical methylation reactions.
Anti-obesity in veterans: In U.S. Veterans, 5-amino-1MQ administration resulted in significant weight loss without adverse side effects (clinical observation data).
Potential metabolic benefits: NNMT inhibition has been linked to improved insulin sensitivity and reduced inflammation. NNMT is implicated in type 2 diabetes pathophysiology (Liu et al., 2021, BioMed Research International).
Non-stimulant: Unlike ephedrine, caffeine, or clenbuterol — 5-amino-1MQ does not stimulate the CNS. No jitteriness, insomnia, or cardiovascular stimulation.

Clinical Evidence Summary

Research Pipeline

Preclinical
Animal
Phase I
Phase II
Phase III
Approved

0

Total Studies

0

Human Studies

- Neelakantan et al. (2018) — 'Selective and membrane-permeable small molecule inhibitors of nicotinamide N-methyltransferase reverse high fat diet-induced obesity in mice.' Key paper establishing 5-amino-1MQ as a viable NNMT inhibitor for obesity (Biochem Pharmacol, PMC 5826726).

- Liu et al. (2021) — 'Roles of Nicotinamide N-Methyltransferase in Obesity and Type 2 Diabetes.' Comprehensive review of NNMT as a therapeutic target (BioMed Research International, PMC 8337113).

- Real-world clinical data from U.S. Veterans showing significant weight loss without adverse effects (observational/clinic data, not formal RCT).

- **Clinical trial status: **No registered Phase I/II/III clinical trials. Research is primarily pre-clinical (animal and cell studies). NNMT as a drug target is gaining academic interest.

Key Studies / PubMed References

NADmetabolism enzyme NNMT in cancer-associated fibroblasts drives tumor progression and resistance to immunotherapy by modulating macrophages in urothelial bladder cancer.

Review

Yang M, Wang B, Hou W, et al. · Journal for immunotherapy of cancer · 2024

PMID: 39067875

Reduced calorie diet combined with NNMT inhibition establishes a distinct microbiome in DIO mice.

Animal Study

Dimet-Wiley A, Wu Q, Wiley JT, et al. · Scientific reports · 2022

PMID: 35013352

Small molecule inhibitor of nicotinamide N-methyltransferase shows anti-proliferative activity in HeLa cells.

In Vitro

Akar S, Duran T, Azzawri AA, et al. · Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology · 2021

PMID: 33645410

Side Effects & Safety

Animal studies: No observable adverse effects at therapeutic doses in mice. 5-amino-1MQ did not impact cell viability in 3T3-L1 pre-adipocytes at 10 μM concentrations.
Community-reported: Generally well tolerated. Some users report mild GI discomfort, headache, or dizziness. These are uncommon and usually transient.
Theoretical concerns: NNMT plays roles beyond adipose tissue (liver, brain, muscle). Long-term systemic NNMT inhibition effects are unknown. Methylation balance disruption is a theoretical risk.
Contraindications: Pregnancy, lactation. Unknown interactions with other drugs affecting methylation pathways. Caution in liver disease (NNMT is highly expressed in the liver).

Known Interactions

No curated interaction entry is live for 5-amino-1MQ yet.

Until the interaction table is fully populated, use the interaction checker and related peptides below to explore adjacent compounds and likely research pairings.

Frequently Asked Questions

Research Disclaimer

This page is for research and educational purposes only. The information presented is based on published scientific literature and does not constitute medical advice, diagnosis, or treatment recommendations. 5-amino-1MQ is not approved by the FDA for human therapeutic use. Always consult a qualified healthcare professional before making any health-related decisions. The studies referenced are linked to their original PubMed sources for verification.