Side-by-side · Research reference

PE 22-28vsSermorelin

Side-by-side comparison across mechanism, dosage, evidence, side effects, administration, and stack synergies. Citations on every claim where available.

AAnimal-StrongHUMAN-REVIEWED16/47 cited

BPhase 3HUMAN-REVIEWED14/43 cited

PE 22-28

TREK-1 Antagonist · Pre-Clinical

0.12 nMTREK-1 IC50Djillani 2017

7 AAPeptide lengthDjillani 2017

AnimalEvidence stage

IP · SQ · Once Daily (animal models)Djillani 2017 Pietri 2019

Sermorelin

GHRH 1-29 fragment · Short-acting

100–500 mcgPer doseMolteno 2013

Phase 3Evidence levelWalker 1994 Molteno 2013

~12 minHalf-lifeMolteno 2013

SQ · Pre-sleep · 1×/day

01Mechanism of Action

Parameter

PE 22-28

Sermorelin

Primary target

TREK-1 two-pore-domain potassium channelDjillani 2017 Ma 2020

Pituitary GHRH receptorWalker 1994

Pathway

TREK-1 channel blockade → Neuronal membrane depolarisation → Enhanced hippocampal excitability → Increased neuroplasticity

GHRH-R → Gαs → cAMP → PKA → GH vesicle exocytosisWalker 1994

Downstream effect

Antidepressant-like activity in forced swim test and tail suspension test; reduced A1-like reactive astrocyte activation; neuroprotection via NF-κB pathway modulationDjillani 2017 Cong 2023 Wu 2021

Pulsatile GH release; subsequent IGF-1 elevationMolteno 2013

Feedback intact?

N/A — direct ion channel blockade; not receptor-mediated endocrine axis

Yes — short pulse preserves feedback

Origin

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 2017 Mazella 2018

Unmodified active 29-AA fragment of human GHRH (1-44)Walker 1994

Antibody development

Not reported in animal studies

—

02Dosage Protocols

Parameter

PE 22-28

Sermorelin

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.

—

Frequency

Once daily

Sustained antidepressant effect over 7+ days.

Once daily, pre-sleep

Onset (animal)

Within hours (acute); full effect 4–7 days

—

Duration (animal)

7–28 days testedQi 2018 Pietri 2019

—

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.

—

Evidence basis

Multiple rodent RCTs; behavioral + electrophysiology endpointsDjillani 2017 Qi 2018 Wu 2021

Phase 3 (Geref pediatric); clinical practiceWalker 1994 Molteno 2013

Standard dose

—

100–500 mcg per injectionMolteno 2013

Lower / starter dose

—

100 mcg per dose

Duration

—

8–12 weeks per cycle

Reconstitution

—

Bacteriostatic water

Timing

—

Pre-sleep, fasted preferred

Half-life

—

~12 min (plasma)Molteno 2013

Shorter than tesamorelin (~26 min) — simpler GHRH analogue.

04Side Effects & Safety

Parameter

PE 22-28

Sermorelin

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

—

Injection site reaction

—

Mild erythema, transient pain

Flushing / headache

—

Common transient effect

IGF-1 elevation

—

Modest at standard doses

Cancer risk

—

Contraindicated in active malignancy (GH/IGF-1 axis)

Pregnancy / OB

—

Avoid

Glucose handling

—

Generally neutral

Absolute Contraindications

PE 22-28

·Human use — no clinical safety data available

Sermorelin

·Active malignancy
·Pregnancy / breastfeeding
·Disrupted hypothalamic-pituitary axis

Relative Contraindications

PE 22-28

·Cardiac arrhythmia or channelopathy (theoretical TREK-1 cardiac role)

Sermorelin

·Untreated diabetes

05Administration Protocol

Parameter

PE 22-28

Sermorelin

1. Animal protocol (IP)

Dissolved in sterile saline or vehicle. Intraperitoneal injection, 0.3–3 µg/kg body weight. Once daily administration in rodent behavioral studies.

Add 2 mL bacteriostatic water to 5 mg vial → 2.5 mg/mL = 250 mcg per 0.1 mL.

2. Stability

Shorter peptide length (7 AA) confers improved plasma stability vs 17-AA spadin. Exact storage conditions not detailed in published protocols.Djillani 2017

SQ — abdomen or thigh. Rotate sites.

3. BBB penetration

Enhanced CNS bioavailability vs full spadin, likely due to smaller size. Mechanism (passive diffusion vs active transport) not fully characterized.

Pre-sleep, fasted.

4. Human formulation

Not established — peptide synthesis methods for research use only. No pharmaceutical-grade formulation available.

Lyophilised: room temp, light-protected. Reconstituted: refrigerate ≤30 days.

5. Needle

—

29–31G, 4–8 mm insulin syringe.

06Stack Synergy

PE 22-28

— no documented stacks

Sermorelin

+ Ipamorelin

Strong

View Ipamorelin →

Sermorelin (GHRH analogue) and ipamorelin (selective GHRP) form the prototypical GHRH+GHRP dual-axis stack at the lowest cost. Both peak within 30 min and produce a sharp physiological GH pulse without cortisol/prolactin elevation.

Sermorelin: 200–300 mcg SQ · pre-sleep
Ipamorelin: 200–300 mcg SQ · same injection
Primary benefit: Pulsatile GH stimulation, recovery, body composition

Raun 1998 Walker 1994