Side-by-side · Research reference

DihexavsMelanotan-II

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

AAnimal-StrongHUMAN-REVIEWED7/28 cited

BPhase 1HUMAN-REVIEWED9/43 cited

Dihexa

Angiotensin IV Analogue · Pre-Clinical

Pre-clinicalDevelopment stage

Rodent onlyEvidence basisBenoist 2014

HGF/c-MetTarget systemWright 2015

Not established — animal studies only

Melanotan-II

MC1R + MC4R agonist · Tanning + sexual response

0.25–1.0 mgPer doseDorr 1996

Phase 1Evidence levelDorr 1996

~1 hrHalf-life

SQ · Abdomen · Loading 5–7 days, then maintenance

01Mechanism of Action

Parameter

Dihexa

Melanotan-II

Primary target

c-Met receptor (HGF receptor tyrosine kinase)

MC1R (skin) + MC3R + MC4R (CNS sexual / appetite)Dorr 1996

Pathway

HGF/c-Met receptor activation → downstream signaling cascade → synaptogenesis and dendritic arborization

MC1R agonism → melanocyte tyrosinase → eumelanin synthesis. MC4R → autonomic sexual arousal centresDorr 1996 Simerly 2023

Downstream effect

Induction of dendritic arborization, synapse formation, neurogenesis, and neuroprotection in rodent models

Skin darkening, photo-protection, increased sexual desire / spontaneous erectionDorr 1996

Feedback intact?

—

Origin

Small-molecule angiotensin IV analogue designed to activate HGF/c-Met systemWright 2015

Cyclic 7-AA modified α-MSH analog; designed at University of ArizonaDorr 1996

Antibody development

—

02Dosage Protocols

Parameter

Dihexa

Melanotan-II

Human dosing

Not established — no human trials

—

Animal studies

Mouse/rat models only — dosing not translatable to humans

—

Evidence basis

Pre-clinical / Rodent models

Phase 1 + anecdotalDorr 1996

Clinical status

No Phase 1, 2, or 3 trials published

—

Loading phase

—

0.25–0.5 mg/day SQ × 5–7 daysDorr 1996

Builds up to visible tan.

Maintenance

—

0.5–1.0 mg 1–2×/week

After visible tan develops; supports with UV exposure.

Frequency

—

Daily during loading; 1–2× per week maintenance

Lower / starter dose

—

0.1 mg / day

Conservative starter — assess tolerability for nausea.

Duration

—

8–12 weeks per cycle

Reconstitution

—

Bacteriostatic water; protect from light

Timing

—

Evening preferred (24h tan-development cycle)

Half-life

—

~1 hour plasma; effects on melanocytes persist days

04Side Effects & Safety

Parameter

Dihexa

Melanotan-II

Human safety data

None available — no human clinical trials

—

Theoretical c-Met risks

c-Met receptor activation has been implicated in tumorigenesis; unknown cancer risk profile

—

Pre-clinical tolerability

Not systematically reported in available studies

—

Nausea

—

Common, especially loading phase

Flushing

—

Common transient

Spontaneous erection

—

Common in men — MC4R cross-effectDorr 1996

Increased mole / freckle pigmentation

—

Existing moles darken; new lesions possible

Melanoma risk

—

Theoretical concern — increased melanocyte activity; CAUTION in melanoma history

Appetite suppression

—

MC4R-mediated; mild

Pregnancy / OB

—

Contraindicated

Absolute Contraindications

Dihexa

·Not approved for human use — research compound only

Melanotan-II

·History of melanoma or atypical mole syndrome
·Pregnancy / breastfeeding
·Active uncontrolled hypertension

Relative Contraindications

Dihexa

·Theoretical contraindication: active or history of malignancy (c-Met pathway involvement in cancer)

Melanotan-II

·Significant freckling / dysplastic nevus
·Personal or family melanoma history

05Administration Protocol

Parameter

Dihexa

Melanotan-II

1. Human administration

No established protocol. Dihexa has not been tested in human subjects. Animal studies used various routes (typically subcutaneous or intraperitoneal in rodents) not translatable to clinical use.

Add 2 mL bacteriostatic water to 10 mg vial → 5 mg/mL = 500 mcg per 0.1 mL. Light-protected.

2. Legal status

Pre-clinical research compound. Not approved by FDA or any regulatory authority for human use.

SQ — abdomen. Rotate sites.

3. Timing

—

Evening preferred. UV exposure (sunlight or tanning bed) helps develop tan.

4. Storage

—

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

5. Needle

—

29–31G insulin syringe.