Overview

PT-141 (Bremelanotide) is a synthetic peptide that was developed from the tanning peptide Melanotan II. During trials of Melanotan II, researchers noticed an unexpected side effect: increased sexual arousal. This led to the development of PT-141, which was optimized specifically for sexual function.

In 2019, the FDA approved PT-141 under the brand name Vyleesi for treatment of Hypoactive Sexual Desire Disorder (HSDD) in premenopausal women, making it the first FDA-approved medication of its kind.

Key Characteristics

Origin: Derived from Melanotan II
Classification: Melanocortin receptor agonist (MC3R/MC4R)
FDA Status: Approved as Vyleesi for female HSDD
Unique Feature: Works through CNS, not vascular system
Mechanism: Central nervous system arousal, not peripheral blood flow

How It Differs from Viagra/Cialis

| Feature | PT-141 | PDE5 Inhibitors (Viagra/Cialis) | |---------|--------|--------------------------------| | Mechanism | Central (brain) | Peripheral (blood flow) | | Effect | Increases desire | Increases erection ability | | Gender | Works for both sexes | Primarily male-focused | | Onset | 45 min | 30-60 min | | Mental component | Yes (arousal) | No (mechanical only) |

Mechanism

Primary Mechanisms

1. Melanocortin Receptor Activation

PT-141 activates melanocortin receptors in the brain:

MC4R: Primary target for sexual function
MC3R: Secondary target, modulates feeding/energy
Located in hypothalamus and limbic system
Affects pathways controlling sexual response

2. Dopamine Pathway Modulation

The melanocortin system interacts with dopamine:

Increases dopamine release in reward centers
Enhances motivation and desire
Creates genuine psychological arousal
Not dependent on physical stimulation

3. Hypothalamic Activation

Works in the brain's "control center":

Activates sexual arousal circuits
Modulates hormonal signaling
Affects both psychological and physical responses
Creates a more "natural" arousal experience

Why This Matters

Unlike blood flow medications:

Works when psychological desire is absent
Effective for both men and women
Addresses the "wanting" not just the "doing"
Can help when stress/anxiety blocks arousal

Research

Research Note: PT-141 has completed clinical trials and received FDA approval, giving it more human data than most peptides.

Female HSDD (FDA Approved)

RECONNECT Trials

Phase 3 trials showed:

Significant increase in sexual desire
Improved satisfying sexual events
Reduced distress related to low desire
Effects noted within 45 minutes

Statistics

25% of patients reported meaningful improvement
Approximately 1 additional satisfying event per month
Effects persist for several hours

Male Sexual Dysfunction

Erectile Dysfunction Studies

Research indicates:

Effective when PDE5 inhibitors fail
Works particularly well for psychogenic ED
Can help men with diabetes-related ED
May be effective for men on antidepressants

2025 Research Updates

Recent studies exploring:

Combination therapy with PDE5 inhibitors
Use in post-prostatectomy patients
Effects on ejaculatory disorders

Comparison to Melanotan II

While both affect melanocortin receptors:

PT-141 is more selective for sexual effects
Less tanning effect than Melanotan II
Lower nausea incidence
Shorter duration of action

Dosing

Disclaimer: PT-141 is FDA-approved for female HSDD under prescription. Off-label use should be discussed with a healthcare provider. All other dosing information is for research reference only.

Research Protocols

Protocol	Dose	Frequency	Duration
Female (FDA Approved)	1.75 mg	45 min before activity	As needed (max 1/24hr)
Male (Research)	1-2 mg	45 min before activity	As needed
Low-Dose Start	0.5 mg	Test dose	Single use
Intranasal (Research)	10-20 mg spray	As needed	As needed

Administration Notes

Timing

Administer 45-60 minutes before desired effect
Effects can last 6-12 hours
Do not use more than once in 24 hours
Not designed for daily use

Subcutaneous Injection

Inject into abdomen or thigh
Rotate injection sites
Use insulin syringe for precision

Dose Adjustment

Start low (0.5 mg) to assess tolerance
Nausea is dose-related
Maximum recommended: 1.75 mg (FDA)
Higher doses don't necessarily improve effect

Important Restrictions

FDA Guidelines (Vyleesi)

No more than 8 doses per month
Not for daily use
Wait 24 hours between doses

Reconstitution

Typically supplied as lyophilized powder
Reconstitute with bacteriostatic water
Store refrigerated after reconstitution
Stable for 4-6 weeks

Pharmacokinetics

Absorption

Subcutaneous: Peak levels in 1-2 hours
Bioavailability approximately 100%

Distribution

Crosses blood-brain barrier
Concentrates in CNS target areas
Volume of distribution suggests wide tissue distribution

Metabolism

Metabolized by hydrolysis
Multiple metabolites identified
No significant CYP450 interactions

Elimination

Half-life: 2.7 hours
Primarily renal excretion
No accumulation with appropriate spacing

Safety

Known Side Effects

Common (>10%)

Nausea (40% - most common, dose-related)
Flushing/hot flashes (20%)
Headache (11%)
Injection site reactions

Less Common (1-10%)

Fatigue
Dizziness
Vomiting
Hyperpigmentation (with repeated use)
Elevated blood pressure (temporary)

Management of Nausea

Take with food
Start with lower dose
Use anti-nausea medication if needed
Usually decreases with experience

Contraindications

Absolute Contraindications:

Uncontrolled hypertension
Cardiovascular disease
Pregnancy or breastfeeding

Relative Contraindications:

Controlled hypertension (monitor closely)
History of melanoma (theoretical concern)
Patients prone to nausea

Blood Pressure Warning: PT-141 can transiently increase blood pressure. Those with cardiovascular disease or uncontrolled hypertension should not use this peptide.

Drug Interactions

Avoid combination with:

Naltrexone (blocks effects)
Blood pressure medications (monitor)
Other melanocortin agents

Use caution with:

Alcohol (may worsen nausea, BP effects)
Medications that lower blood pressure

Monitoring

Before Use

Blood pressure measurement
Cardiovascular risk assessment
Discussion of realistic expectations

During Use

Blood pressure monitoring (first few uses)
Side effect tracking
Efficacy assessment

Long-Term Considerations

Skin pigmentation changes
Blood pressure trends
Treatment effectiveness over time

Regulatory

Current Status

| Region | Status | |--------|--------| | United States | FDA-approved (Vyleesi) for female HSDD | | European Union | Not approved | | WADA | Not prohibited | | Male Use | Off-label/research |

Legal Considerations

FDA-approved medication (for specific indication)
Requires prescription for approved use
Research chemical for other uses
Not controlled/scheduled
Insurance coverage limited

Clinical Outlook

PT-141 represents a breakthrough in sexual medicine:

First CNS-targeting sexual dysfunction treatment
Potential for expanded indications
Research ongoing for male-specific approval
May combine with other treatments
Growing acceptance in sexual health medicine

References

[1] Clayton AH, et al.. Bremelanotide for female sexual dysfunctions in premenopausal women: the RECONNECT studies. Journal of Clinical Psychiatry (2016)

[2] Kingsberg SA, et al.. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder. Obstetrics & Gynecology (2019)

[3] Diamond LE, et al.. An effect on the subjective sexual response in premenopausal women with sexual arousal disorder by bremelanotide. Journal of Sexual Medicine (2006)

[4] FDA. Vyleesi (bremelanotide) Prescribing Information. Food and Drug Administration (2019)

[5] Sexual Medicine Research. Melanocortin Agonists in Sexual Dysfunction: 2025 Update. Journal of Sexual Medicine (2025)