PT-141  ·  Bremelanotide  ·  MC3R/MC4R Agonist  ·  RUO

Desire starts
in the brain.
Not the body.

A cyclic heptapeptide derived from alpha-MSH that activates melanocortin receptors in the hypothalamus and limbic system - the first compound ever approved that targets sexual desire through brain pathways rather than peripheral vascular mechanisms.

FDA Approved as Vyleesi® MC3R / MC4R Agonist CNS Mechanism Cyclic Heptapeptide Not a PDE5 Inhibitor ≥99% HPLC

Compound characterisation data. For Research Use Only. Not the FDA-approved drug Vyleesi®.

Manufactured in US

US-formulated & filled

Endotoxin Tested

<0.05 EU/mL verified

Independently Tested

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The Origin Story

Found while
studying
tanning.

PT-141 wasn’t designed to target sexual desire. It emerged from research into skin pigmentation - specifically from studies of Melanotan II, a melanocortin agonist being investigated for tanning. Researchers noticed an unexpected side effect: sexual arousal. That serendipitous observation led Palatin Technologies to engineer a cleaner derivative, eventually yielding the first FDA-approved drug targeting desire through brain pathways.

MT2

1990s

Melanotan II - Tanning Research

Researchers studying melanocortin agonists for skin pigmentation notice an unexpected side effect: spontaneous sexual arousal in study participants. The compound lacked specificity and caused significant nausea.

PT

2000

PT-141 Synthesized - Palatin Technologies

Palatin Technologies engineers a cyclic heptapeptide derived from Melanotan II by removing the C-terminal amide. This eliminates the potent tanning effect while preserving and refining the sexual response activity. PT-141 = cleaner, more selective.

Ph2

2004–2008

Formulation Change

Early formulation work moved away from the nasal route following blood-pressure findings, and the development programme was redirected toward a different indication.

FDA

June 2019

Vyleesi® Approved as a Pharmaceutical

Bremelanotide was approved under the brand name Vyleesi® as a finished pharmaceutical. That approval covers the licensed medicine only, and does not extend to this research material.

Molecular Identity

Cyclic Heptapeptide Structure

Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH

Cyclic N-acetylated D-Phe pharmacophore

7 AA

Cyclic heptapeptide

1025 Da

C50H68N14O10

10 nM

MC4R binding affinity (Ki)

2.7 hr

Plasma half-life

CAS Number

189691-06-3

Palatin Technologies · FDA Vyleesi prescribing information 2019 · ChemicalBook CAS 189691-06-3

The Key Distinction

Brain, not
blood vessels.

Every established sexual health compound before PT-141 worked peripherally - dilating blood vessels, increasing blood flow to genital tissue. PT-141 is mechanistically different: it operates centrally, in the hypothalamus and limbic system, activating the neural circuits that generate desire itself. This distinction is why it works in PDE5 inhibitor-resistant populations and why it addresses desire (not just physical response).

The FDA prescribing information notes that the exact mechanism by which Vyleesi improves HSDD is not fully characterized - an honest acknowledgment that MC4R agonism’s downstream pathway to desire is complex. What is established: MC4R knockout mice show markedly impaired sexual function, and MC4R is concentrated in hypothalamic and limbic regions governing arousal and motivation.

MC4R knockout mice show severely impaired erectile function in males and reduced sexual receptivity in females - supporting MC4R as a receptor of interest in centrally-regulated arousal research
PT-141 showed 62% improvement in sildenafil-resistant erectile dysfunction patients vs 21% placebo (Safarinejad & Hosseini 2008) - confirming a mechanism independent of the PDE5/vasodilatory pathway
MC4R agonism activates dopaminergic signaling in reward circuits - the neurobiological substrate of desire, motivation, and arousal rather than physical response

Mechanism Comparison

Property
PT-141
PDE5 Inhibitors
Site of action
CNS / Brain
Peripheral
Primary target
MC3R / MC4R
PDE5 enzyme
Addresses desire
✓ Yes
✕ No
Requires arousal
Not required
Required
PDE5-resistant cases
✓ Active
✕ Fails
FDA approved women
✓ HSDD (2019)
Not indicated
Dopamine pathway
✓ Activated
Not directly
Research context only.
Mechanism of Action

MC4R → cAMP →
dopamine → arousal.

PT-141 activates melanocortin-3 and melanocortin-4 receptors in the hypothalamus and limbic system. MC4R is a Gαs-coupled GPCR - receptor binding raises intracellular cAMP, which activates downstream signaling cascades that influence dopaminergic neurotransmission and nitric oxide release. The downstream pathway from MC4R to desire involves neural circuits in the hypothalamic preoptic area, nucleus accumbens, and amygdala.

1
Entry

MC3R / MC4R Binding → Gαs Activation

PT-141 binds MC3R and MC4R in the hypothalamus and limbic regions. MC4R is highly expressed in the hypothalamic preoptic area and paraventricular nucleus - both established regulators of sexual behavior. Ki = 10 nM at human MC4R (competitive binding against NDP-α-MSH in HEK-293 cells). MC4R couples to Gαs protein.

2
Signaling

cAMP Accumulation → PKA → Downstream Cascades

Gαs activation → adenylate cyclase → ↑cAMP → PKA. PT-141 induces cAMP accumulation in hMC4R-expressing HEK-293 cells (documented pharmacological assay endpoint). Parallel activation of phospholipase C → IP3/DAG → Ca2+ also documented for MC3R.

3
Neural

Dopamine Release → Reward Circuit Activation

MC4R activation in hypothalamic circuits enhances dopaminergic neurotransmission - the same reward circuitry underlying motivation and desire. Dopamine pathway activation in the nucleus accumbens and mesolimbic system generates the subjective experience of wanting/desire. NO (nitric oxide) release also documented as a downstream mediator.

4
Arousal

Limbic System Activation → Sexual Arousal & Desire

Neural signal propagation through amygdala, nucleus accumbens, and cortex generates desire and arousal independent of genital stimulation or vascular events. In rodent models, PT-141 has been studied for arousal-related behaviours through activation of neurons in brain regions associated with sexual function.

Research Endpoint Areas

HSDD
Women

Hypoactive Sexual Desire Disorder - Female Models

MC4R agonism in female models is an area of ongoing research interest. FSDS-DAO and FSFI are standard validated instruments used in this research domain.

ED
Men

Erectile Dysfunction - Including PDE5-Resistant

MC4R agonism is studied as a central pathway distinct from the peripheral vascular mechanism of PDE5 inhibitors. Research interest centres on models where the vascular route is not the limiting fDE5-resistant population (Safarinejad & Hosseini 2008). IIEF and nocturnal penile tumescence are standard endpoints.

MC4R
Pharma

Melanocortin Receptor Pharmacology - CNS Biology

PT-141 is the primary research tool for MC4R pharmacology studies. cAMP HTRF assay in MC4R-expressing HEK-293 cells. Receptor binding competition assays against NDP-α-MSH. MC4R knockout phenotype comparison. Behavioral paradigms in rodent models.

SSRI
Related

SSRI-Induced Sexual Dysfunction Models

PT-141 is studied in models of SSRI-induced sexual dysfunction - a common adverse effect of antidepressants that operates through serotonergic suppression of MC4R signaling. Research into melanocortin system modulation as a reversal mechanism for iatrogenic sexual dysfunction.

Compound Profile

Full specification.

Molecular and analytical data from Eon Peptides batch records.

7 AA
Cyclic heptapeptide
Lactam ring structure
1025 Da
Molecular weight
C50H68N14O10
10 nM
MC4R binding (Ki)
HEK-293 competitive binding
2.7 hr
Plasma half-life
Range 1.9–4.0 hr

Long-term

-20°C

Lyophilized sealed. Stable 24 months. Avoid frost-free freezers.

Short-term

2–8°C

Sealed and desiccated. Appropriate for near-term holding.

Solubility

Water-soluble

Soluble in water and in PBS at pH 7.0–7.4.

Avoid

Oxidants

Protect from light. Cyclic peptide backbone is sensitive to oxidative degradation.

For Research Use Only - Not for Human Consumption. Not Vyleesi® or any approved drug. Supplied exclusively for in vitro laboratory research by qualified researchers.

Common NamePT-141 / Bremelanotide
Brand NameVyleesi® (bremelanotide injection) - FDA-approved drug. Not Eon Peptides’ product.
SequenceAc-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
CAS Number189691-06-3
Molecular FormulaC50H68N14O10
Molecular Weight1,025.16 Da
StructureCyclic heptapeptide · lactam ring · N-terminal acetylated norleucine · D-Phe pharmacophore
Primary TargetsMC3R, MC4R (melanocortin receptors) - hypothalamus and limbic system
Receptor AffinityMC4R Ki = 10 nM (HEK-293 competitive binding vs NDP-α-MSH)
SignalingMC4R → Gαs → ↑cAMP → PKA → dopamine → arousal circuits
PK Peak (Tmax)~1 hr reported for the licensed pharmaceutical
Plasma t½2.7 hr (range 1.9–4.0 hr)
Bioavailability~100% reported for the licensed pharmaceutical
FormLyophilized powder · sealed glass vial
Purity≥99% HPLC · Mass Spec verified · 6-panel COA · Freedom Diagnostic
Endotoxin<0.05 EU/mL · LAL-tested · Freedom Diagnostic
RegulatoryRUONot Vyleesi® - In Vitro Research Use Only