Side-by-side · Research reference

AdamaxvsPE 22-28

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

AAnimal-StrongHUMAN-REVIEWED20/47 cited

BAnimal-StrongHUMAN-REVIEWED16/47 cited

Adamax

ACTH(4-10) Analogue · Russian Nootropic

1.4×BDNF protein ↑Dolotov 2006

3×BDNF mRNA (exon III)Dolotov 2006

1.6×trkB phosphorylationDolotov 2006

Intranasal · Research Use Only

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

01Mechanism of Action

Parameter

Adamax

PE 22-28

Primary target

Melanocortin receptors (MC-Rs) in hippocampus and cortex

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

Pathway

ACTH(4-10) fragment → MC-R binding → BDNF/trkB upregulation → neurotrophic signaling

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

Downstream effect

Increased hippocampal BDNF expression, trkB tyrosine phosphorylation, enhanced conditioned avoidance learning, circadian rhythm normalizationDolotov 2006 Arushanian 2008

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

Feedback intact?

Non-endocrine — devoid of adrenal axis effectsvan 1978

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

Origin

ACTH(4-10) fragment with modified amino acid sequence at positions 8, 9, 10Teter 2001

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

Antibody development

—

Not reported in animal studies

02Dosage Protocols

Parameter

Adamax

PE 22-28

Animal dose (rat)

50 mcg/kg body weightDolotov 2006

Single intranasal application; produced maximal BDNF response.

—

Route

IntranasalDolotov 2006 Smolnik 2000

—

Frequency

Single-dose or chronic administration protocols

Chronic dosing normalized circadian rhythms; single-dose produced acute BDNF elevation.

Once daily

Sustained antidepressant effect over 7+ days.

Human dose (exploratory)

Not established — limited human data

ACTH(4-10) and analogs dosed 30–60 mcg intranasally in early human studies.

—

Evidence basis

Animal (rodent, rabbit) studies; minimal human RCT data

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

Timing

Variable — chronic administration for circadian effects

—

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

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.

04Side Effects & Safety

Parameter

Adamax

PE 22-28

Cardiovascular effects

ACTH(4-10) fragments may have pressor and cardioaccelerator actions at high dosesGruber 1984

Effects attenuated by α/β-receptor antagonists; observed at 30–1000 nmol/kg IV in rats.

—

Natriuretic effect

ACTH(4-10) exhibited natriuretic activity at lower doses (7 nmol/kg)Gruber 1984

—

Behavioral suppression

Suppression of aggression, reduced orientation-cognition reactions in rabbitsTeter 2001

May reflect anxiolytic or stress-dampening profile.

—

Long-term safety

Unknown — chronic human safety data lacking

Unknown — longest animal study 28 days

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

Adamax

·Pregnancy and lactation (precautionary; no data)
·Active cardiovascular instability (due to potential pressor effects)

PE 22-28

·Human use — no clinical safety data available

Relative Contraindications

Adamax

·Hypertension (monitor BP if using higher doses)
·Renal impairment (natriuretic effects may alter electrolyte balance)

PE 22-28

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

05Administration Protocol

Parameter

Adamax

PE 22-28

1. Reconstitution (if lyophilised)

Add sterile water or bacteriostatic water to lyophilised vial per manufacturer guidance. Roll gently — do not shake. Ensure clarity before use.

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

2. Route

Intranasal administration is the primary route in animal and exploratory human studies. Delivered via nasal spray or dropper to ensure mucosal absorption.Dolotov 2006 Smolnik 2000

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

Variable. Single-dose protocols for acute cognitive tasks; chronic daily dosing for circadian rhythm normalization and sustained neuroprotection.

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

4. Storage

Lyophilised: room temperature, light-protected. Reconstituted: refrigerate 2–8 °C, use within manufacturer-specified timeframe.

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

06Stack Synergy

Adamax

+ Semax

Moderate

View Semax →

Both Adamax and Semax are ACTH(4-10)-derived nootropics acting via melanocortin receptors and BDNF upregulation. Adamax has distinct amino acid modifications at positions 8-10, potentially offering complementary receptor binding profiles or metabolic stability. Stacking may amplify neurotrophic signaling and cognitive enhancement, though direct synergy studies are absent. Theoretical multi-pathway benefit.

Adamax: Research dose intranasal
Semax: 300–600 mcg intranasal
Frequency: Once daily, morning or pre-cognitive task
Primary benefit: Enhanced BDNF upregulation, cognitive performance, neuroprotection

PE 22-28

— no documented stacks