PT-141
Bremelanotide (Vyleesi) — a cyclic heptapeptide derived from Melanotan II, engineered to selectively activate MC4R in the brain for sexual arousal. FDA-approved for hypoactive sexual desire disorder (HSDD) in premenopausal women. Uniquely acts on central nervous system desire pathways rather than peripheral vascular mechanisms like PDE5 inhibitors, making it the first drug to treat the desire component of sexual dysfunction.
Typical Dosage
FDA-approved: 1.75 mg subcutaneous at least 45 minutes before anticipated sexual activity. Maximum 1 dose per 24 hours, maximum 8 doses per month. Off-label (men): similar dosing subcutaneous as needed.
Administration
Subcutaneous injection (autoinjector)
Mechanism of Action
PT-141 (bremelanotide) is a cyclic heptapeptide derived from Melanotan II through targeted structural modification to shift receptor selectivity toward MC4R and away from MC1R. It was developed specifically to capture the sexual arousal effects observed with MT-II while minimizing the unwanted tanning (MC1R-mediated) effects. The result is a peptide that acts primarily on the central nervous system rather than peripheral vasculature.
PT-141 activates melanocortin 4 receptors (MC4R) in key brain regions involved in sexual function, particularly the medial preoptic area, the paraventricular nucleus of the hypothalamus, and descending autonomic pathways. MC4R is a Gs-coupled GPCR that increases intracellular cAMP, activating neural circuits that regulate sexual desire, arousal, and physiological sexual response. This central mechanism is fundamentally different from PDE5 inhibitors (sildenafil, tadalafil), which work peripherally by enhancing nitric oxide-mediated vasodilation in penile and clitoral erectile tissue. PDE5 inhibitors improve the mechanical response to arousal but do not affect desire; PT-141 acts upstream, enhancing the desire and arousal signals that originate in the brain.
In women with hypoactive sexual desire disorder (HSDD), PT-141 activates these hypothalamic sexual arousal circuits to increase desire, sexual arousal, and genital response. The nausea experienced by approximately 40% of users is attributed to MC4R activation in the area postrema (the vomiting center in the brainstem), which lies outside the blood-brain barrier and is therefore accessible to circulating peptides. The transient blood pressure elevation results from sympathetic nervous system activation downstream of hypothalamic MC4R signaling. PT-141 retains some residual MC1R activity, which can produce mild facial flushing, but at therapeutic doses the tanning effect is minimal compared to MT-II.
Regulatory Status
FDA approved (2019) as Vyleesi for HSDD in premenopausal women. Palatin Technologies. Off-label use in men through compounding pharmacies.
Risks & Safety
Common: nausea (40% of patients), facial flushing, headache, injection site reactions. Serious: transient blood pressure increases (average 6/3 mmHg), focal hyperpigmentation with repeated use. Rare: severe nausea requiring anti-emetic, significant hypertensive episode. Contraindicated in uncontrolled hypertension and cardiovascular disease. FDA approved.
Research Papers
4Published: October 23, 2025
Abstract
Vasomotor symptoms (VMS) and decreased libido are common menopausal symptoms. Patients with breast cancer receiving endocrine therapy experience new or worsening menopausal symptoms. Pharmacologic therapy for VMS has been centered on selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors, gabapentin, and clonidine. These therapeutic options fall short in obtaining adequate symptom relief, illustrating a therapeutic gap in efficacious treatment modalities. There are no historical systemic treatment options for low libido.
Published: January 18, 2026
Abstract
To conduct a systematic review and meta-analysis of treatments for female sexual desire, arousal, and orgasmic dysfunction in patients without sexual pain conditions.
Published: August 9, 2025
Abstract
Despite considerable advances in the systemic delivery of peptides, their susceptibility to gastrointestinal degradation and high molecular weight, which restricts permeability across biological barriers, remain obstacles to oral administration. As a result, most peptide therapies rely on injections to achieve therapeutic effects. Recent studies on a bioinspired suction patch demonstrated positive effects in vivo with three peptides - desmopressin, semaglutide, and teriparatide - yet materials used for patch fabrication were non-degradable. In this work, a more sustainable patch alternative is introduced by replacing previously used materials with biodegradable polymers, aiming for degradation of the patch after removal to reduce environmental impact. A scalable mold casting process was employed to thermally crosslink synthesized and functionalized copolyesters, yielding the desired devices. Mechanical testing across various materials and shapes identified the best-performing polymer, while its degradation was confirmed in both aqueous medium and simulated waste. An ex vivo model using porcine buccal tissue validated the functionality of biodegradable patches, showing enhanced permeation of a poorly permeable dye when combined with a chemical permeation enhancer. In beagle dogs, the bioavailability of semaglutide (4.11 kDa) was substantially improved compared to the commercially available tablet, with an application time of only 10 min. Additionally, the patch achieved a relative bioavailability of 26% for bremelanotide (1.03 kDa) compared to subcutaneous administration. This work underscores the potential of replacing silicone devices with biodegradable alternatives, providing a more sustainable approach for peptide delivery via the buccal suction patch.
Published: April 13, 2025
Abstract
Erectile dysfunction (ED) pathophysiology involves complex interactions between vasculogenic, hormonal, and neurological mechanisms, with endothelial dysfunction and oxidative stress playing crucial roles. There is growing interest in intravenous (IV) peptides and amino acids as potential therapeutic options for ED treatment.
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