Side-by-side · Research reference
5-Amino-1MQvsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongAUTO-DRAFTED8/38 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
5-Amino-1MQ
NNMT inhibitor · Methylation / SAM modulation
Oral · Once daily fasted
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
5-Amino-1MQ
PE 22-28
Primary target
Nicotinamide N-methyltransferase (NNMT)Neelakantan 2018
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
NNMT inhibition → preserved cellular SAM + NAD⁺ → restored methylation balance + ↑ thermogenic gene expressionNeelakantan 2018
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Reversal of HFD-induced obesity in murine models; improved metabolic profileNeelakantan 2018
Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017Cong 2023Wu 2021
Feedback intact?
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N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Selective small-molecule inhibitor designed in academic medicinal chemistry programsNeelakantan 2018
Synthetic truncation of spadin (PE 12-28), itself derived from the sortilin propeptide C-terminus. Residues 22-28: Val-Val-Arg-Gly-Trp-Leu-Arg.Djillani 2017Mazella 2018
Antibody development
—
Not reported in animal studies
02Dosage Protocols
Parameter
5-Amino-1MQ
PE 22-28
Frequency
Once daily, fasted
Once daily
Sustained antidepressant effect over 7+ days.
Lower / starter dose
50 mg / day
—
Evidence basis
Animal-strong; no human RCT dataNeelakantan 2018
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Duration
8–12 weeks per cycle
—
Form
Oral capsule
—
Timing
Morning fasted preferred
—
Half-life
Hours (estimated; no human PK published)
—
Animal dose (antidepressant)
—
0.3–3 µg/kg IP
Effective in forced swim test, tail suspension test, CUMS models.
Animal dose (neuroprotection)
—
0.03 µg/kg IPPietri 2019
Low-dose TREK-1 activation post-stroke for 7 days, then high-dose blockade.
Onset (animal)
—
Within hours (acute); full effect 4–7 days
Comparison to fluoxetine
—
PE 22-28 outperforms fluoxetine in CUMS-sensitive rats by day 7
Chronic administration shows superior long-term efficacy.
Human equivalent (extrapolated)
—
Not established — no clinical trials
Allometric scaling from rodent data unavailable.
04Side Effects & Safety
Parameter
5-Amino-1MQ
PE 22-28
GI symptoms
Mild nausea (anecdotal)
—
Methylation disruption
Theoretical risk if NNMT is over-inhibited (B vitamin metabolism)
—
Long-term safety
Unknown — no human trials
Unknown — longest animal study 28 days
Cancer risk
Unclear — NNMT also studied in oncology contexts
—
Pregnancy / OB
Avoid
—
Drug interactions
Theoretical with niacin / B-vitamin supplements
—
Toxicity (animal)
—
No adverse effects reported at therapeutic doses
Cardiovascular (theoretical)
—
TREK-1 expressed in cardiac tissue; arrhythmia risk unclear
Weight change
—
Not reported in animal studies
Neurological
—
No seizures or behavioral abnormalities noted
Absolute Contraindications
5-Amino-1MQ
- ·Pregnancy / breastfeeding
- ·Active malignancy
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
5-Amino-1MQ
- ·Methylation-sensitive conditions (MTHFR mutation)
- ·Concurrent niacin / NAD+ precursor supplementation (theoretical interference)
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
5-Amino-1MQ
PE 22-28
1. Form
Oral capsule. No injection.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Administration
Take with water, fasted preferred.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Timing
Morning fasted.
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Storage
Room temp ≤25 °C, dry place.
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
5. Caveat
Monitor B-vitamin status with chronic use.
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