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PT-141

PT-141 (bremelanotide) is a synthetic peptide analog of alpha-melanocyte-stimulating hormone ((\alpha )-MSH). It acts as a melanocortin receptor agonist, specifically targeting receptors in the brain to increase sexual desire and arousal, rather than targeting blood flow like traditional ED medications.

Key Benefits

  • May support increased sexual desire and arousal response in both men and women
  • Commonly researched for improving erectile function and sexual performance
  • May help support sexual satisfaction by acting on central nervous system pathways
  • Research suggests potential benefits for addressing certain forms of hypoactive sexual desire disorder
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FDA-Approved Uses

✅ FDA-APPROVED INDICATION:

1. Hypoactive Sexual Desire Disorder (HSDD) in Premenopausal Women
Vyleesi (bremelanotide) is FDA-approved for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.

Specific approval criteria (per FDA label):

  • Acquired HSDD: Developed in a woman who previously had no sexual desire problems
  • Generalized HSDD: Occurs regardless of type of stimulation, situation, or partner
  • Causes marked distress or interpersonal difficulty
  • NOT due to: co-existing medical or psychiatric condition, relationship problems, medication or drug use
  • On-demand use: Take at least 45 minutes before sexual activity; not a daily medication

NOT indicated for (per FDA label):

– Postmenopausal women (not studied in this population)
– Men (not approved; off-label use exists)
– Enhancing sexual performance (not an aphrodisiac for performance)

Common off-label uses (not FDA-approved):

  • HSDD in postmenopausal women
  • Erectile dysfunction in men (particularly PDE5-inhibitor-resistant cases)
  • SSRI-induced sexual dysfunction
  • Sexual dysfunction in men with spinal cord injury

Trade Names in USA and Manufacturers

FDA-Approved Brand:

  • Vyleesi (bremelanotide injection 1.75 mg/0.3 mL)
  • Manufacturer: Cosette Pharmaceuticals, Inc.
  • (Originally developed by Palatin Technologies; previously distributed by AMAG Pharmaceuticals prior to acquisition by Cosette)
  • Formulation: Sterile, clear solution in a pre-filled syringe in a single-dose autoinjector
  • Inactive ingredients: 2.5% glycerin, sterile water for injection, HCl or NaOH for pH adjustment

Off-label compounded versions:
– Available from licensed 503A compounding pharmacies with physician prescription
– Also available as grey-market research peptide (lyophilized powder)

Molecular identity: Synthetic cyclic heptapeptide (7 amino acids in closed ring)
IUPAC name: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH
MW: ~1,025 Daltons
Derived from: Melanotan II (which was derived from alpha-MSH)

Dosage

FDA-Approved Dosing (Vyleesi):

  • Dose: 1.75 mg subcutaneously via autoinjector
  • Timing: At least 45 minutes BEFORE anticipated sexual activity
  • Frequency: Maximum 1 dose per 24-hour period
  • Maximum 8 doses per month
  • Location: Abdomen or thigh
  • Discontinue if no improvement in sexual desire after 8 weeks of use

Autoinjector instructions:

  • Remove cap, place on thigh or abdomen
  • Press button firmly until click is heard
  • Hold in place for 5 seconds
  • Discard after single use; do not reuse

Nausea management:
Physician may pre-prescribe ondansetron (Zofran) or another antiemetic if nausea is anticipated based on history

Off-label male dosing (not FDA-approved; from clinical practice):
0.5–2 mg SC, 30–60 min before activity
Lower doses often used for men to reduce side effects while maintaining effect

Pricing

Brand-name list price (Vyleesi, 2026):
Per autoinjector (1 dose): ~$100–$150
Per month (8 doses maximum): ~$800–$1,200

With commercial insurance + Vyleesi savings card:
As low as $0 for eligible commercially insured patients
(Cosette Pharmaceuticals offers a savings program; verify eligibility)

Patient assistance program:
Palatin/Cosette offers a patient assistance program for uninsured patients who meet income eligibility criteria

Compounded bremelanotide (with prescription, 503A pharmacy):
~$100–$250/month (significantly cheaper than branded Vyleesi)
Note: Compounded versions are not FDA-reviewed for bioequivalence to Vyleesi

Research peptide vendors:
~$30–$80 per vial (lyophilized powder, research use only)

Coverage by Insurance Type

Medicare Part D
For HSDD: Covered under Part D (FDA-approved drug for enrolled indication) ✅
Verify formulary and tier placement with specific plan

Tips

  • Vyleesi is the ONLY FDA-approved on-demand treatment for HSDD in premenopausal women. It is the first and only drug in its class with this indication.
  • Take at least 45 minutes before activity — earlier (60–90 min) may provide optimal effect for some users.
  • The Cosette savings card may reduce cost to $0/month for commercially insured patients.
  • Nausea affects ~40% of users with the FIRST dose but typically improves with subsequent doses. Ask your doctor about pre-medicating with ondansetron.
  • Blood pressure increases transiently by ~6 mmHg systolic for up to 12 hours — if you have hypertension or cardiovascular risk, discuss with your doctor before use.
  • Focal hyperpigmentation (darkening of face, gums, or breasts) occurs in ~1% of users with repeated use.
  • Do NOT use with oral naltrexone (Vivitrol, Naltrexone for alcohol/opioid use disorder).

Side Effects

From FDA prescribing information, Phase 3 RECONNECT trials, and post-marketing surveillance:

Very common (>10%):

  • Nausea: 40% of patients (most common side effect; severe in ~5%; mild-moderate in majority; improves with subsequent doses)
  • Flushing: 20.3%
  • Injection site reactions (bruising, pain, erythema): 13.2%
  • Headache: 11.3%

Common (2–10%):
– Vomiting: 4.8%
– Cough: 3.3%
– Fatigue: 3.2%
– Hot flashes: 2.7%
– Paresthesia: 2.6%
– Dizziness: 2.2%
– Nasal congestion: 2.1%

Cardiovascular (requires monitoring):
– Transient blood pressure increase: Peak ~+6 mmHg systolic / +3 mmHg diastolic at 2–4 hours post-dose; returns to baseline within 12 hours
– Transient heart rate decrease: Up to 5 bpm
– ~1% of patients had individual readings ≥180/110 mmHg

Skin (persistent risk with repeated use):
– Focal hyperpigmentation (darkening of face, gingiva/gums, breasts): ~1% of patients receiving up to 8 doses/month; risk higher with darker skin tones and more frequent use. Resolution NOT confirmed in all patients after stopping.

Rare/serious:
– Hepatotoxicity: One case of acute icteric hepatitis reported in open-label extension (10 doses over 1 year); considered a possible rare cause of liver injury (NCBI LiverTox score D)
– Animal reproductive toxicity: Fetal harm in dogs and mice at doses >16x human dose — use effective contraception during treatment

Contraindications

Per FDA Vyleesi prescribing information (approved label):

Contraindicated:
– Uncontrolled hypertension: Due to transient BP elevation with each dose
– Known cardiovascular disease or high cardiovascular risk: FDA label recommends against use; assess CV risk before and during treatment
– Concurrent use with orally administered naltrexone-containing products: Bremelanotide significantly reduces oral naltrexone absorption — avoid combination (relevant for patients on Vivitrol for alcohol or opioid use disorder)
– Pregnancy: Animal studies show fetal harm; women should use effective contraception during treatment. Discontinue if pregnancy occurs.

Not established / use with caution:
– Postmenopausal women: Not studied in Phase 3 trials (off-label only)
– Men: Not approved per FDA label
– Elderly patients: Safety and efficacy not established
– Pediatric patients: Not studied
– Patients with hepatic impairment: Limited data; bremelanotide metabolized by hydrolysis / renal clearance; hepatic impairment may have limited impact but data is incomplete
– Patients on antihypertensive medications: BP-lowering effect may interact; monitor
– Breastfeeding: No adequate studies; weigh risk vs. benefit

Pharmacology

Bremelanotide (PT-141) is a synthetic cyclic heptapeptide (7-amino-acid closed ring) and active metabolite of melanotan II, which itself was derived from alpha-melanocyte-stimulating hormone (α-MSH). Structural designation: Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH. MW ~1,025 Daltons (bremelanotide free base); bremelanotide acetate MW ~1,025 + acetate. The cyclic structure provides enhanced metabolic stability vs. linear peptides. Formulated as sterile solution (pH adjusted), 1.75 mg/0.3 mL autoinjector. Pharmacokinetics (SC injection): Bioavailability ~100%; Tmax ~1 hour (range 0.5–1.0h); plasma protein binding 21%; half-life 2.7 hours (range 1.9–4.0h); metabolized via peptide bond hydrolysis; excreted 64.8% urine / 22.8% feces. Onset of desired effect: ~45–60 minutes post-injection. Duration of effect: ~4–6 hours.

Mechanism of action

Bremelanotide is a non-selective melanocortin receptor (MCR) agonist:

Receptor activation order of potency: MC1R > MC4R > MC3R > MC5R > MC2R

At therapeutic doses, MC1R and MC4R binding are most clinically relevant:

1. MC4R (primary for HSDD mechanism):

MC4R neurons are distributed throughout the CNS, particularly in the medial preoptic area of the hypothalamus and limbic system. This activation in hypothalamic circuits is thought to increase dopamine signaling in the mesolimbic pathway, increasing sexual motivation and desire.

2. MC1R (pigmentation side effect mechanism):

MC1R is expressed on melanocytes in the skin and mucosa.
Binding activates melanogenesis (melanin production) — explaining focal hyperpigmentation in ~1% of users.

3. Cardiovascular effects:

Transient BP increase and heart rate decrease may be mediated through central MCRs involved in cardiovascular regulation and/or peripheral MC1R activation.

4. Gastric motility:

Slows gastric emptying via peripheral MCR activation — basis for nausea and reduced oral drug absorption.

Result Claims By Different Companies

Palatin Technologies / Cosette Pharmaceuticals (based on Phase 3 RECONNECT trials):

– RECONNECT 1 and RECONNECT 2 (identical design, n=1,267 total, 52 weeks):
Co-primary endpoints: Change in sexual desire score (FSDS-DAO item 13) and change in distress score (FSDS-DAO item 14)
Results vs. placebo:
→ Statistically significant improvement in sexual desire score in both trials
→ Statistically significant reduction in distress associated with low sexual desire
→ Numerically but NOT statistically significantly higher number of satisfying sexual events in RECONNECT 1; statistically significant in RECONNECT 2

– Palatin Technologies’ stated claim: ‘Vyleesi is the first and only as-needed treatment approved by the FDA for HSDD in premenopausal women.’

– Off-label male data (clinical research, not approved):
→ Phase 1/2 intranasal studies (Diamond et al.): 34% of bremelanotide-treated men with ED achieved erection sufficient for intercourse vs. 9% placebo
→ Combination with sildenafil (25 mg): Consistently stronger erectile response than either drug alone in research data

Disclaimer

This content about “PT-141” is for informational and educational purposes only, is not medical advice, does not replace consultation with a licensed healthcare professional, and affiliate links may result in compensation at no additional cost to you.