PT-141 – Lessico dei peptidi

PT-141

Bremelanotide

Clinicamente consolidataOrmonale· Bremelanotide

PT-141 (bremelanotide) is a synthetic cyclic heptapeptide and an analog of the endogenous hormone α-MSH that acts as an agonist at melanocortin receptors. It emerged from the melanocortin research program around Melanotan II and is the only peptide from this program to have been approved as an injectable; Melanotan I (afamelanotide) reached approval as an implant. On June 21, 2019, the FDA granted marketing authorization (NDA 210557) under the brand name Vyleesi for the treatment of acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women. In research, the substance appears mainly in the context of melanocortin receptor pharmacology and the central nervous regulation of sexual function.

Pubblicato il 12 ago 2026

Meccanismo d'azione

Bremelanotide is a non-selective agonist of the melanocortin receptor family. According to the US prescribing information (Vyleesi USPI, section 12.1), it activates several receptor subtypes with the potency order MC1R, MC4R, MC3R, MC5R, MC2R, with binding to MC1R and MC4R being most relevant at therapeutic concentrations. MC4R-expressing neurons are present in many regions of the central nervous system, and MC4R activation is considered the candidate mechanism for the observed effects on sexual desire; the prescribing information explicitly states, however, that the mechanism by which the substance improves HSDD symptoms is unknown. MC1R activation on melanocytes explains the focal hyperpigmentation observed in the trials. Pharmacokinetically, the prescribing information (section 12.3) describes a terminal half-life of about 2.7 hours (range 1.9 to 4.0 hours) after a single subcutaneous dose, a clearance of 6.5 L/h and a volume of distribution of about 25 L; the molecule is metabolized via hydrolysis of the amide bonds of the cyclic peptide.

Stato delle evidenze

Bremelanotide was developed through a formal clinical program to approval. The basis was the two identical, randomized, double-blind, placebo-controlled phase 3 trials of the RECONNECT program (NCT02333071 and NCT02338960; Kingsberg et al., 2019), with a total of 1,267 randomized premenopausal women with HSDD (635 active, 632 placebo) across a 24-week double-blind phase plus a 52-week open-label extension (Simon et al., 2019). Both co-primary endpoints were met with statistical significance in both trials, but the mean effects were moderate: the FSFI desire score (scale 1.2 to 6.0) rose by a mean of 0.5 and 0.6 points on active treatment versus 0.2 on placebo, and the FSDS-DAO Q13 distress score (scale 0 to 4) fell by 0.7 versus 0.4 points. Nausea was the most common adverse reaction at 40 percent versus 1.3 percent on placebo; the prescribing information additionally describes transient blood pressure increases after each dose and lists uncontrolled hypertension and known cardiovascular disease as contraindications. The FDA approval (NDA 210557, June 21, 2019) applies exclusively to acquired, generalized HSDD in premenopausal women and, according to Drugs@FDA, is currently held by Cosette Pharmaceuticals. All of these data come from the finished pharmaceutical product under controlled trial conditions; they cannot be extrapolated to other contexts of use, other populations, or unregulated research material.

Domande sullo stato della ricerca

What has PT-141 (bremelanotide) been investigated for clinically?: Bremelanotide was tested in the RECONNECT program in two identical placebo-controlled phase 3 trials in premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), each using on-demand subcutaneous self-administration before anticipated sexual activity. On this basis, the FDA granted approval as Vyleesi in 2019. The approval explicitly does not cover postmenopausal women or men and is not intended to enhance sexual performance. Beyond that, the substance serves in research as a tool for studying melanocortin receptors, in particular MC4R in the central nervous system.
What is the state of the evidence on PT-141?: With two completed phase 3 trials, a 52-week open-label extension and an FDA approval, the evidence base is comparatively extensive for a peptide of this class. At the same time, the mean effect sizes in the pivotal trials were moderate, and nausea occurred in 40 percent of treated participants. In men, bremelanotide was tested in an earlier intranasal development program for erectile dysfunction in randomized, placebo-controlled trials (for example Safarinejad and Hosseini, 2008); that program was discontinued, in part over blood pressure increases, and never led to an approval. No marketing authorization therefore exists for men, and the Vyleesi approval is a regulatory statement for a narrowly defined indication and population; the data cannot be extrapolated to other contexts of use or to unregulated research material.

Fonti

Kingsberg et al., Obstet Gynecol 2019 (RECONNECT, Phase 3)DOI: 10.1097/AOG.0000000000003500PMID: 31599840
Simon et al., Obstet Gynecol 2019 (offene Verlängerung)DOI: 10.1097/AOG.0000000000003514PMID: 31599847
FDA Approval Package NDA 210557 (Vyleesi, 21.06.2019)
Vyleesi US Prescribing Information (FDA, 2019)
Hadley & Dorr, Peptides 2006 (Melanocortin-Historie)DOI: 10.1016/j.peptides.2005.01.029PMID: 16412534
Safarinejad & Hosseini, J Urol 2008 (intranasale ED-Studie, Männer)DOI: 10.1016/j.juro.2007.10.063PMID: 18206919

PT-141

Bremelanotide

Clinicamente consolidataOrmonale· Bremelanotide

Pubblicato il 12 ago 2026

Meccanismo d'azione

Stato delle evidenze

Domande sullo stato della ricerca

What has PT-141 (bremelanotide) been investigated for clinically?

Bremelanotide was tested in the RECONNECT program in two identical placebo-controlled phase 3 trials in premenopausal women with acquired, generalized hypoactive sexual desire disorder (HSDD), each using on-demand subcutaneous self-administration before anticipated sexual activity. On this basis, the FDA granted approval as Vyleesi in 2019. The approval explicitly does not cover postmenopausal women or men and is not intended to enhance sexual performance. Beyond that, the substance serves in research as a tool for studying melanocortin receptors, in particular MC4R in the central nervous system.

What is the state of the evidence on PT-141?

With two completed phase 3 trials, a 52-week open-label extension and an FDA approval, the evidence base is comparatively extensive for a peptide of this class. At the same time, the mean effect sizes in the pivotal trials were moderate, and nausea occurred in 40 percent of treated participants. In men, bremelanotide was tested in an earlier intranasal development program for erectile dysfunction in randomized, placebo-controlled trials (for example Safarinejad and Hosseini, 2008); that program was discontinued, in part over blood pressure increases, and never led to an approval. No marketing authorization therefore exists for men, and the Vyleesi approval is a regulatory statement for a narrowly defined indication and population; the data cannot be extrapolated to other contexts of use or to unregulated research material.