Side-by-side · Research reference

AdamaxvsP21

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-MechanisticHUMAN-REVIEWED8/36 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

P21

CNTF-Derived Neuropeptide · Animal Model Evidence

CNTFR/gp130Primary receptorGuo 2022

Animal onlyEvidence level

NeurogenesisPrimary effectJia 2020 Mottolese 2024

SQ · Site unspecified · Frequency unknown

01Mechanism of Action

Parameter

Adamax

P21

Primary target

Melanocortin receptors (MC-Rs) in hippocampus and cortex

CNTF receptor alpha (CNTFRα) / LIF receptor (LIFR) / gp130 complex on neural stem cells

Pathway

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

CNTF mimetic → CNTFRα/LIFR/gp130 heterotrimer → JAK/STAT3 signaling → neurogenesis, stem cell proliferation, neuroprotection

Downstream effect

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

Increased neural stem cell self-renewal, globose basal cell activation (Mash1+ cells), olfactory sensory neuron regeneration, hippocampal neurogenesis, neuroprotection in developmental disorders

Feedback intact?

Non-endocrine — devoid of adrenal axis effectsvan 1978

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Origin

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

Small-molecule peptide mimetic derived from full-length ciliary neurotrophic factor (CNTF), designed to retain receptor activation with improved pharmacokineticsMottolese 2024

Antibody development

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02Dosage Protocols

Parameter

Adamax

P21

Animal dose (rat)

50 mcg/kg body weightDolotov 2006

Single intranasal application; produced maximal BDNF response.

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Route

IntranasalDolotov 2006 Smolnik 2000

Presumed subcutaneous or intraperitoneal (animal studies)

Frequency

Single-dose or chronic administration protocols

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

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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

Animal models only

CDKL5 KO mice, methimazole-induced olfactory injury, CNTF-/- knockout models.Mottolese 2024 Cox 2026 Jia 2020

Timing

Variable — chronic administration for circadian effects

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Human dosing

—

No established protocol

No clinical trial data available.

Animal models (mice)

—

Dose and route not specified in abstractsMottolese 2024 Jia 2020

In vitro and in vivo studies demonstrate efficacy; precise dosing protocols not disclosed.

Duration

—

Not specified

04Side Effects & Safety

Parameter

Adamax

P21

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.

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Natriuretic effect

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

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Behavioral suppression

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

May reflect anxiolytic or stress-dampening profile.

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Long-term safety

Unknown — chronic human safety data lacking

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Human safety data

—

None available

No clinical trials in humans.

Animal tolerability

—

Well-tolerated in mouse models; no toxicity reported in available abstracts

Theoretical risks

—

Uncontrolled stem cell proliferation, immune response to peptide, unknown long-term CNS effects

Absolute Contraindications

Adamax

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

P21

·Use in humans not validated

Relative Contraindications

Adamax

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

P21

·Active malignancy (theoretical — neurotrophic signaling may affect tumour growth)
·Pregnancy or lactation (no safety data)

05Administration Protocol

Parameter

Adamax

P21

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.

Not established. No FDA approval, no clinical trial data.

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

In vivo studies used systemic administration (route not specified in abstracts) in mouse models of neurodegeneration, olfactory injury, and CDKL5 deficiency disorder. In vitro studies used primary cell cultures.

3. Timing

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

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4. Storage

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

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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

P21

— no documented stacks