Side-by-side · Research reference
HGH Fragment 176-191vsPE 22-28
Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.
AAnimal-StrongHUMAN-REVIEWED28/59 cited
BAnimal-StrongHUMAN-REVIEWED16/47 cited
HGH Fragment 176-191
GH Fragment · Pre-Clinical
SQ · IP (animal) · Oral (tested)
PE 22-28
TREK-1 Antagonist · Pre-Clinical
IP · SQ · Once Daily (animal models)Djillani 2017Pietri 2019
01Mechanism of Action
Parameter
HGH Fragment 176-191
PE 22-28
Primary target
Beta-3 adrenergic receptors on adipocytesHeffernan 2001
TREK-1 two-pore-domain potassium channelDjillani 2017Ma 2020
Pathway
Fragment → β3-AR upregulation → Enhanced lipolytic sensitivityHeffernan 2001
TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity
Downstream effect
Increased lipolysis and beta-3 AR mRNA expression without IGF-1 axis activation
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?
N/A — does not interact with GH/IGF-1 axis
N/A — direct ion channel blockade; not receptor-mediated endocrine axis
Origin
Synthetic peptide derived from hGH residues 176-191; AOD9604 includes N-terminal tyrosine (177-191)Cox 2015
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 available studies
Not reported in animal studies
02Dosage Protocols
Parameter
HGH Fragment 176-191
PE 22-28
Animal dose (IP)
Not specified (14-day chronic administration)Heffernan 2001
Obese mice, daily IP injection.
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Human equivalent dose
Not established — no published human RCTs
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Frequency
Once daily (animal models)
Once daily
Sustained antidepressant effect over 7+ days.
Evidence basis
Animal studies only
Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017Qi 2018Wu 2021
Detection window
50 pg/mL LOD in urine; stable metabolite extends detectionCox 2015
WADA-banned; anti-doping testing available.
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Oral bioavailability
Demonstrated efficacy in animal oral administrationNg 2000
Potential for oral therapeutic development.
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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.
03Metabolic / Fat Loss Evidence
Parameter
HGH Fragment 176-191
PE 22-28
Weight gain reduction
50% reduction vs control (15.8 ± 0.6 g vs 35.6 ± 0.8 g)Ng 2000
Obese Zucker rats, 19 days oral administration.
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Body fat reduction
Significant decrease in body weight and body fat in obese mice (14 days)Heffernan 2001
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Lipolytic activity
Increased adipose tissue lipolytic activityNg 2000
Direct measurement in treated animals.
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Insulin sensitivity
No adverse effect — euglycemic clamp confirmedNg 2000
Contrasts with intact hGH diabetogenic effects.
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IGF-1 impact
No elevation — fragment does not activate GH/IGF-1 axis
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Beta-3 AR dependency
Effect abolished in β3-AR knockout miceHeffernan 2001
Confirms β3-AR as primary mechanism.
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Human evidence
None published — pre-clinical only
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04Side Effects & Safety
Parameter
HGH Fragment 176-191
PE 22-28
Human safety data
Not available — no published human trials
—
Metabolic profile
Six metabolites identified; CRSVEGSCG most stableCox 2015
Detection window implications for doping control.
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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
Long-term safety
—
Unknown — longest animal study 28 days
Absolute Contraindications
HGH Fragment 176-191
- ·Competitive athletes (WADA-banned)Cox 2015
PE 22-28
- ·Human use — no clinical safety data available
Relative Contraindications
HGH Fragment 176-191
- ·Absence of human safety data — experimental use only
PE 22-28
- ·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)
05Administration Protocol
Parameter
HGH Fragment 176-191
PE 22-28
1. Route
Subcutaneous injection primary route in research context. Oral administration demonstrated efficacy in animal models at 500 mcg/kg.
Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.
2. Frequency
Once daily dosing used in animal studies. Timing not specified; GH-independent mechanism suggests flexibility.
Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017
3. Duration
Animal protocols: 14–19 days. Human duration not established — no published trials.
Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.
4. Storage
Lyophilized peptide storage per standard peptide protocols. Metabolite stability suggests refrigerated reconstituted solution viable.
Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.
5. Detection
Detectable in urine via SPE-LC-MS at 50 pg/mL LOD. Extended detection window via stable metabolite CRSVEGSCG.Cox 2015
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