PT-141: Bremelanotide

What Is PT-141?

PT-141 (bremelanotide) is a synthetic peptide and melanocortin receptor agonist. Originally developed from the tanning peptide Melanotan II, it was found to have sexual arousal effects independent of its tanning properties. In 2019, it became FDA-approved under the brand name Vyleesi® for premenopausal women with hypoactive sexual desire disorder (HSDD).

PT-141 is unique as the first medication to work through the nervous system (rather than vascular effects like PDE5 inhibitors) to enhance sexual desire.

Development History

PT-141's journey from tanning peptide to sexual health drug:

• 1990s: Melanotan II studied for tanning; sexual effects noticed
• Early 2000s: Palatin Technologies develops PT-141 without tanning effects
• 2007: Initial nasal spray development halted (blood pressure concerns)
• 2019: FDA approval as subcutaneous injection for female HSDD

Mechanism of Action

Melanocortin Receptor Activation

PT-141 works through melanocortin receptors in the nervous system:

• Primarily activates MC4R and MC3R receptors
• These receptors are found in the hypothalamus and limbic system
• Modulates neural pathways involved in sexual arousal
• Affects both desire and physiological arousal

Central vs Peripheral Action

Unlike PDE5 inhibitors (Viagra, Cialis):

• Works centrally in the brain, not peripherally on blood vessels
• Targets desire and arousal pathways
• Effective even when physical arousal mechanisms are intact
• May address psychological components of desire

Neurological Effects

• Activates dopaminergic pathways
• Modulates hypothalamic sexual response centers
• May affect reward and motivation circuits

Clinical Trial Results

RECONNECT Trials

The pivotal trials for FDA approval:

Measure	PT-141	Placebo	Significance
Desire (FSFI)	+0.6	+0.3	Significant
Distress reduction	Improved	Less improved	Significant
Satisfying events	Increased	Less increase	Significant

Research in Men

Studies have also examined PT-141 in male sexual dysfunction:

• Produced erections in men who didn't respond to Viagra
• Effective in psychogenic erectile dysfunction
• Not currently approved for men
• Research ongoing

Approved Use

Side Effects

Common Side Effects

• Nausea (40% — most common, usually mild)
• Flushing (21%)
• Injection site reactions (13%)
• Headache (11%)
• Fatigue

Important Warnings

• Transient blood pressure increases
• Contraindicated in uncontrolled hypertension
• Contraindicated in cardiovascular disease
• May cause skin hyperpigmentation (darkening) with repeated use
• Caution with naltrexone (may reduce efficacy)

PT-141 vs Melanotan II

Feature	PT-141	Melanotan II
FDA Status	Approved (Vyleesi)	Not approved
Tanning effect	Minimal/none	Significant
Sexual effects	Primary effect	Secondary effect
Structure	Linear (cyclic core)	Cyclic
Receptor profile	MC3R/MC4R focused	Broader MC1R activity

Key Published Research

Year	Focus	Key Finding	Reference
2000	Initial human studies	Pro-erectile effects in men	Wessells et al.
2008	Female studies	Increased arousal in women	Diamond et al.
2016	RECONNECT trials	Phase 3 efficacy data	Kingsberg et al.
2019	FDA approval package	Full safety/efficacy data	Palatin/FDA

Research Considerations

Areas of ongoing interest:

• Male sexual dysfunction applications
• Postmenopausal women (not currently approved)
• Combination with other approaches
• Alternative delivery methods
• Long-term safety data collection

Summary

PT-141 (bremelanotide) represents a unique approach to sexual health — targeting central nervous system pathways involved in desire rather than peripheral vascular mechanisms. Its FDA approval for female HSDD established melanocortin agonism as a viable therapeutic pathway for sexual dysfunction. The compound's ability to enhance desire through neurological mechanisms continues to drive research interest for both male and female applications.