PT-141

Overview

PT-141 (Bremelanotide) is a synthetic peptide analog of α-melanocyte-stimulating hormone (α-MSH). Originally developed from Melanotan II research, it gained FDA approval in 2019 as Vyleesi for the treatment of hypoactive sexual desire disorder (HSDD) in premenopausal women.

Unlike PDE5 inhibitors (Viagra, Cialis), PT-141 works through the central nervous system, making it unique among sexual dysfunction treatments. It acts on melanocortin receptors in the brain to influence sexual desire rather than the physical mechanics of arousal.

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

Mechanism of Action

PT-141 works through activation of melanocortin receptors:

MC4R Activation

• Primary target: Melanocortin-4 receptor (MC4R)
• Located in hypothalamus and limbic system
• Involved in sexual behavior and arousal pathways
• Modulates dopamine and oxytocin release

MC1R Activity

• Some activity at MC1 receptors
• Responsible for tanning/pigmentation effects
• Less potent than Melanotan II at this receptor

Central Nervous System Effects

• Acts on brain regions involved in sexual arousal
• Increases dopamine in reward pathways
• May influence oxytocin release
• Works independent of vascular effects

Distinction from PDE5 Inhibitors

• Does not directly affect blood flow
• Works on desire rather than physical function
• Effective in both sexes (though only approved for women)
• Does not require sexual stimulation to work

Research Summary

RECONNECT Trials (Phase 3)

RECONNECT Study (n=1,247)

• Premenopausal women with HSDD
• Primary endpoint: Satisfying sexual events (SSEs)
• Secondary: Female Sexual Function Index (FSFI)

Results:

Earlier Clinical Studies

Men with Erectile Dysfunction

• Phase 2 studies showed efficacy
• 33% response rate (erection sufficient for intercourse)
• Development discontinued for this indication

Women (Pre-approval)

• Multiple studies demonstrated desire improvement
• Patient satisfaction higher than placebo
• Effects onset within 1-2 hours

Key Findings

• Approximately 8% more patients responded vs placebo
• Effects observed regardless of testosterone levels
• No cardiovascular effects like PDE5 inhibitors
• Works on desire rather than just function

Pharmacokinetics

Common Protocols

FDA-Approved Dosing (Vyleesi)

For HSDD in Premenopausal Women:

• Dose: 1.75mg subcutaneous injection
• Timing: At least 45 minutes before anticipated sexual activity
• Frequency: Maximum one dose per 24 hours
• Limit: Maximum 8 doses per month

Research Community Protocols

The following represents off-label protocols discussed in research communities.

Men (Off-label):

• 1-2mg subcutaneous
• 30-60 minutes before activity
• Some report lower doses (0.5-1mg) effective

Nasal Administration (Discontinued):

• Earlier research used nasal spray
• Discontinued due to blood pressure concerns
• Injection route now standard

Administration

Vyleesi Auto-injector

• Pre-filled single-dose auto-injector
• 1.75mg per injection
• Subcutaneous injection in abdomen or thigh

Research Use

• Reconstituted lyophilized powder
• Bacteriostatic water typically used
• Subcutaneous injection
• Store reconstituted at 2-8°C

Timing

• Administer at least 45 minutes before activity
• Effects last several hours
• Do not use more than once in 24 hours

Side Effects

Common (>5% incidence)

• Nausea (40% - most common)
• Flushing (20%)
• Injection site reactions (13%)
• Headache (11%)

Less Common

• Fatigue
• Dizziness
• Hot flush
• Facial flushing
• Hyperpigmentation (with repeated use)

Serious/Warnings

• Blood pressure increase: Transient elevation observed
• Focal hyperpigmentation: Darkening of skin, gums, breast areolae
• Contraindicated in uncontrolled hypertension

Nausea Management

• Anti-nausea medication may help
• Often decreases with subsequent doses
• Taking with food may help some users

Interactions

Contraindications

• Uncontrolled hypertension
• Known cardiovascular disease
• Hypersensitivity to bremelanotide

Drug Interactions

• Naltrexone: Reduced efficacy of PT-141
• Other melanocortins: Potential additive effects
• Blood pressure medications: Monitor BP

Precautions

• Cardiovascular disease
• History of hypertension
• Concurrent use of alcohol (may worsen nausea)

Community Insights

The following represents aggregated reports from online communities and should not be considered medical advice or verified claims.

Commonly Reported Experiences

• Nausea is the most frequent complaint
• Many report noticeable increase in desire
• Effects often described as "different" from Viagra
• Some report emotional/mental arousal more than physical
• Onset typically 30-60 minutes

Practical Tips Shared

• Anti-nausea meds (Zofran) commonly mentioned
• Lower doses may reduce nausea while maintaining effect
• Eating light meal beforehand debated
• Some report tolerance with frequent use

Male Use (Off-label)

• Reported effective for erectile dysfunction
• Often described as producing "natural" erections
• Some combine with PDE5 inhibitors
• Spontaneous erections reported

Concerns Discussed

• Nausea limits use for many
• Cost of Vyleesi auto-injector high
• Skin darkening with repeated use
• Some report inconsistent effects

References

1. Clayton AH, et al. Bremelanotide for Female Sexual Dysfunctions in Premenopausal Women: A Randomized, Placebo-Controlled Dose-Finding Trial. Womens Health (Lond). 2016;12(3):325-37. [PMID: 27215442]

2. Kingsberg SA, et al. Bremelanotide for the Treatment of Hypoactive Sexual Desire Disorder: Two Randomized Phase 3 Trials. Obstet Gynecol. 2019;134(5):899-908. [PMID: 31599840]

3. FDA Label - Vyleesi (bremelanotide) injection. Reference ID: 4457810. 2019.

4. Diamond LE, et al. Double-blind, placebo-controlled evaluation of the safety, pharmacokinetic properties and pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in healthy males. Int J Impot Res. 2004;16(1):51-9. [PMID: 14963471]

5. Rosen RC, et al. Bremelanotide: A Melanocortin Receptor Agonist for the Treatment of Hypoactive Sexual Desire Disorder. Expert Opin Investig Drugs. 2017;26(10):1207-1215.

6. Molinoff PB, et al. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003;994:96-102. [PMID: 12851303]