Side-by-side · Research reference

AdamaxvsMOTS-c

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-REVIEWED16/68 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

MOTS-c

Mitokine · Mitochondria-Encoded

5–10 mgWeekly doseLee 2015

AnimalEvidence levelLee 2015 Reynolds 2021

Min–hrsHalf-life

SQ · Variable · 2–3×/week

01Mechanism of Action

Parameter

Adamax

MOTS-c

Primary target

Melanocortin receptors (MC-Rs) in hippocampus and cortex

Mitochondrial 12S rRNA sORF → folate-AICAR-AMPK axisLee 2015

Pathway

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

Folate cycle inhibition → ↑AICAR → AMPK phosphorylation → PGC-1α upregulationLee 2015 Kim 2018

Downstream effect

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

Enhanced fatty acid oxidation, GLUT4-mediated glucose uptake, mitochondrial bioenergetics, anti-inflammationLee 2015

Feedback intact?

Non-endocrine — devoid of adrenal axis effectsvan 1978

Stress-responsive, AMPK-dependent nuclear translocationKim 2018

Origin

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

Endogenous 16-AA mitokine; mtDNA-encoded; declines with age; upregulated by exerciseReynolds 2021

Antibody development

—

02Dosage Protocols

Parameter

Adamax

MOTS-c

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.

2–3× per week

Short half-life may necessitate more frequent dosing for saturation.

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 + anecdotalLee 2015 Reynolds 2021 A first-in-human phase 1 study 2021

Phase 1a/1b CB4211 analog trial completed 2021; no native MOTS-c RCT published.

Timing

Variable — chronic administration for circadian effects

Pre-workout or fasted state preferred

Activity-context amplifies AMPK response.

Standard dose

—

5–10 mg / weekLee 2015

Experimental, extrapolated from animal data. No human RCT-derived dose.

Lower / starter dose

—

2.5–5 mg / week

Recommended due to limited human data.

Duration

—

4–12 weeks (experimental)

Optimal cycle length unknown.

Reconstitution

—

Bacteriostatic water, 1–2 mL

10 mg/mL at 1 mL.

Half-life

—

Minutes to hours (estimated)

Systemically unstable; native MOTS-c PK in humans not fully characterised.

03Metabolic / Fat Loss Evidence

Parameter

Adamax

MOTS-c

Primary fat target

—

Diet-induced / metabolic obesity; systemic fat utilization

Quantified reduction

—

Significant HFD fat gain ↓Lee 2015

Murine models, dose-dependent (5 & 15 mg/kg).

IGF-1 impact

—

No direct IGF-1 pathway; AMPK-mediated

Effect on lean mass

—

High dose significantly ↑ lean mass in mice

Insulin sensitivity

—

Reversed HFD insulin resistance in 7 days (mice)Lee 2015

Triglycerides

—

AMPK-driven FA oxidation suggests TG benefit (not directly measured)

Glucose metabolism

—

Improved glucose tolerance; GLUT4 upregulationLee 2015

Effect reversibility

—

Unknown — no long-term follow-up data

Context dependency

—

No effect in normal-chow mice; requires metabolic stressReynolds 2021

Key publication

—

Lee Cell Metab 2015 · Reynolds Nat Commun 2021 · Kim Cell Metab 2018Lee 2015 Reynolds 2021 Kim 2018

04Side Effects & Safety

Parameter

Adamax

MOTS-c

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

—

Injection site reaction

—

Mild irritation (reported)

Fluid retention / Edema

—

Not reported

Glucose intolerance

—

Improves glucose toleranceLee 2015

Cardiovascular

—

Heart palpitations (anecdotal); cardiac hypertrophy reversed in diabetic rats

Cancer risk

—

Contradictory data — some models suggest pro-proliferative effects

CNS / Neurological

—

Insomnia, headache (anecdotal reports)

GI symptoms

—

Nausea, stomach discomfort (reported)

Antibody formation

—

No data (no long-term human trials)

Pregnancy / OB

—

Avoid — insufficient safety data

Evidence quality

—

Phase 1 analog (CB4211); preclinical; anecdotal humanA first-in-human phase 1 study 2021

Absolute Contraindications

Adamax

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

MOTS-c

·Pregnancy / breastfeeding (insufficient data)

Relative Contraindications

Adamax

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

MOTS-c

·Active cancer or cancer predisposition
·AMPK pathway deficiency (efficacy nullified)
·Use with cancer-promoting medications (theoretical)

05Administration Protocol

Parameter

Adamax

MOTS-c

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.

Add 1–2 mL bacteriostatic water. At 10 mg/vial, 1 mL gives 10 mg/mL concentration. Roll gently to dissolve.

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

Subcutaneous — abdomen, thigh, or deltoid. Rotate sites to avoid lipohypertrophy. Pinch fat layer.

3. Timing

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

Pre-workout or fasted state preferred — metabolic context amplifies AMPK response. 2–3× per week.

4. Storage

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

Lyophilised: room temp, protected from light. Reconstituted: refrigerate, use within 21–30 days. Short systemic stability.

5. Needle

—

27–31G insulin syringe. Short needle (4–6 mm) for SQ delivery. Clean technique mandatory.

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

MOTS-c

+ Ipamorelin

Moderate

View Ipamorelin →

MOTS-c activates AMPK/PGC-1α for mitochondrial efficiency and fatty acid oxidation; ipamorelin stimulates GH for anabolic recovery and sleep depth. Pathways are complementary — MOTS-c handles metabolic flexibility and glucose handling while ipamorelin drives recovery and body recomposition through GH. Theoretical synergy is high; clinical data is lacking.

MOTS-c: 5 mg SQ · pre-workout (2–3×/wk)
Ipamorelin: 200–300 mcg SQ · pre-sleep (daily)
Primary benefit: Metabolic flexibility + GH recovery + ROS reduction