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What Is PT-141? PT-141, also known as bremelanotide, has earned the nickname “female Viagra” due to its previous investigation in phase IIb human clinical trials for treating female hypoactive sexual desire disorder (HSDD). PT-141 is a melanocortin that primarily binds to the melanocortin 4 receptor (MC-4R) and MC-1R. In 2009, PT-141 was also explored as a treatment for acute hemorrhage. PT-141 is derived from another synthetic melanocortin, melanotan 2 (MT-2).

PT-141 Molecular Structure

Sequence: Ac-Nle-Asp(1)-His-D-Phe-Arg-Trp-Lys(1)
Molecular Formula: C50H68N14O10
Molecular Weight: 1025.182 g/mol
PubChem CID: 9941379
CAS Number: 189691-06-3

PT-141 Research PT-141 and Sexual Arousal PT-141 stands out as a unique peptide because it stimulates MC-4R, known for inducing sexual arousal in the central nervous system and influencing sexual behavior. Studies in mice have shown that MC-4R activation leads to sexual arousal and increased copulation in both males and females. Unlike drugs like Viagra, PT-141 works through a different mechanism, making it possible to treat sexual arousal disorders in both men and women arising from causes other than reduced blood flow to the genitals.

A study involving men with erectile dysfunction (ED) who did not respond to sildenafil (Viagra) found that about one-third experienced sufficient erections for sexual intercourse with PT-141 (administered via nasal spray). The trial also showed a strong dose-dependent response, indicating the effectiveness of PT-141 in certain cases. This suggests that PT-141 could provide insights into treating ED when sildenafil has been ineffective and may shed light on central causes of hypoactive sexual desire.

Notably, PT-141 was removed from clinical trials before gaining approval for treating women with HSDD. This decision was made despite positive results, which showed an increase in the number of satisfying sexual events per month and a decrease in female sexual distress scores, all without substantial side effects. Experts in female sexual dysfunction (FSD) expressed disappointment at the drug’s discontinuation. They point to a lack of well-established trial endpoints for FSD and societal biases affecting women’s sexual health as major obstacles hindering the approval of much-needed therapies. They hope for increased attention to this issue and the establishment of clearer FDA guidelines for evaluating therapies like PT-141, which can offer significant benefits. These experts also believe that combining pharmacological treatments with other established approaches for sexual dysfunction may yield synergistic results, with peptides like PT-141 helping to overcome initial barriers and kickstart psychological treatment methods.

In 2017, Phase II Reconnect trials were initiated, partly in response to the outcry over the discontinuation of earlier trials. These new trials used subcutaneous injections of PT-141 for FSD, and the latest version of PT-141, known as Rekynda, may soon be available for use in the United States. This could potentially allow off-label use of PT-141 to treat both male and female sexual dysfunction. These new trials incorporated modified endpoints, which experts in FSD have advocated as beneficial for getting such treatments approved.

PT-141 and Hemorrhage In 2009, PT-141 was slightly modified and investigated as a potential treatment for hemorrhagic shock. Because PT-141 binds to both MC-1R and MC-4R, it reduces ischemia and protects tissues against inadequate blood supply in hypovolemic (hemorrhagic) shock. When administered intravenously, the drug does not produce substantial side effects. It reached phase IIb trials and is referred to as PL-6983 in its modified form.

PT-141 and Infection MC-1R has been found, in a rat model of a specific fungal infection, to possess crucial anti-fungal and anti-inflammatory properties. This discovery is significant because existing anti-fungals have limited mechanisms of action and often cause severe and treatment-limiting side effects in certain patients. Having an alternative treatment for fungal infections could significantly reduce morbidity and mortality, especially in immunocompromised patients.

PT-141 and Cancer MC-1R is an important regulator of DNA repair pathways, making it relevant in cancer treatment and prevention. Research indicates that individuals with MC-1R variants are at increased risk of both basal cell and squamous cell carcinoma. Altered PT-141 may have the potential to correct issues resulting from these variants and prevent or treat these types of cancers.

PT-141 and Weight Loss Studies show that MC-4R plays a critical role in regulating appetite. Peptides like melanotan 2 and PT-141, which activate MC-4R, promote feelings of satiety and reduce total calorie intake. PT-141 also appears to interact with leptin signaling pathways to regulate food intake in a complex manner. This is not surprising, considering that PT-141 is derived from α-MSH, which negatively regulates food intake through interactions with the ghrelin-leptin system.

Animal studies suggest that PT-141 increases energy expenditure by affecting certain energy pathways, leading to an increase in basal metabolism. Research in mice demonstrates that MC-4R activation can enhance thermogenesis, even in mice genetically modified to have deficiencies in the proteins that regulate this process. The outcome is increased calorie burning, even at rest, with most of the calorie expenditure occurring in adipose tissue.

Recent double-blind, randomized, placebo-controlled trials have supported the physiological findings and confirmed that PT-141 results in significant weight loss, primarily due to reduced caloric intake. Subjects given PT-141 lost approximately twice as much weight as those in the placebo group, with an overall reduction of nearly 400 calories per day. The study also indicated a dose-response, with subjects losing more weight when administered PT-141 twice daily compared to once daily. PT-141 and its interactions with melanocortin receptors are currently under active investigation to gain a better understanding of the melanocortin system’s role in weight loss and energy balance.

PT-141 Research Directions While PT-141 has garnered significant attention as a treatment for sexual dysfunction, its potential extends to a wide range of research areas. For instance, MC-4R defects or deficiencies are known causes of obesity and may contribute to up to 6% of early-onset obesity cases. PT-141 offers a unique opportunity to explore this specific obesity cause and potentially uncover intervention pathways. MC-1R plays roles in pain, inflammation, kidney pathology, and infection spread, offering a wealth of research opportunities that PT-141 could help elucidate.

It’s important to note that PT-141 exhibits minimal side effects, low oral bioavailability in mice, and excellent subcutaneous bioavailability. Dosage in mice does not scale to humans. PT-141 available at Peptide Sciences is strictly for educational and scientific research purposes, not for human consumption. Only purchase PT-141 if you are a licensed researcher.