Source: PubChem

 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 and Sexual Arousal

It is the only peptide known for stimulating the MC-4R, a receptor recognized for initiating sexual arousal in the central nervous system, as well as having an effect on sexual behavior. Research on mice has shown that binding to the said receptor through an agonist leads to increased sexual arousal and heightened copulation in male and female subjects alike. It’s important to mention that PT-141 operates differently compared to drugs like Viagra, suggesting its potential as a treatment for sexual arousal disorders in both sexes, including those not influenced by reduced blood flow to the genital area.

In a clinical trial with men experiencing erectile dysfunction (ED) who didn’t respond to Viagra (sildenafil), subjects were administered Pt-141 via nasal spray. Approx. one third of the participants successfully achieved erections sufficient for sexual intercourse. Results of the study suggest a strong correlation between dosage and response, indicating the efficacy of PT-141 in specific instances. These findings show the potential of PT-141 in regard to offering insights into comprehending the main causes of hypoactive sexual desire disorder, while plausibly offering treatment for erectile dysfunction when sildenafil doesn’t prove effective.

Duration of penile base rigidity greater than 60% for placebo compared to various doses of PT-141.
Source: Nature

Prior to receiving approval, PT-141 was interestingly withdrawn from clinical trials. Peptide with a potential for addressing women with hypoactive sexual desire disorder didn’t advance in regards to treating said disorder, despite showing a notable rise in the frequency of satisfying sexual events per month and a reduction in female sexual distress scores. This decision has left many experts in the field of female sexual dysfunction disheartened, and they ascribed it to the lack of established endpoints for FSD trials and societal biases against women’s sexual health. Obstacles as such pose challenges to the approval process for much-needed treatments like PT-141.

Said experts are advocating for raising awareness on the subject and establishing more specific Food and Drug Administration (FDA) guidelines to assess therapies like PT-141 and its benefits. They have said that a combination of therapies could potentially have synergistic effects, and lament the absence of testing pharmacological treatments alongside already established methods for addressing sexual dysfunction. These experts consider peptides like PT-141 as beneficial not only for surmounting initial obstacles, but also for initiating psychological treatment approaches.

In reaction to the outcry over the discontinuation of previous trials, Phase II Reconnect trials were launched in 2017. The trials involve the use of subcutaneous injections of PT-141 to address Female Sexual Dysfunction (FSD). Rekynda is the latest version of PT-141, and it is anticipated to soon be accessible in the United States. This would authorize the off-label use of PT-141 for treating sexual dysfunction in both men and women. The latest trials have introduced modified endpoints, an appreciated development by the experts, since it increases the likelihood of approval for such treatments.

PT-141 and Hemorrhage

Due to its strong binding affinity to MC-1R and MC-4R, PT-141 has shown the capability to mitigate ischemia and protect tissues from inadequate blood supply during hypovolemic (hemorrhagic) shock. This is why in 2009, PT-141 underwent minor adjustments while being studied for its potential hemorrhagic shock treating capability. It’s worth mentioning that there were minimal side effects when the drug was administered intravenously. The new, modified form of PT-141 is now called PL-6983 and it has been assessed in phase IIb trials.

PT-141 and Infection

MC-1R exhibits anti-fungal and anti-inflammatory properties, as it has been observed when studying a rat model with a particular fungal infection. Present anti-fungal treatments have proven to be limiting in their mechanism of action, oftentimes leading to severe side effects in certain individuals, hindering treatment, which is why this discovery proves significant. Alternative methods of treating fungal infections have the potential of substantially lowering morbidity and mortality rates, which can be accentuated in patients with compromised immune systems.

PT-141 and Cancer

The MC-1R receptor holds a pivotal role in activating pathways for DNA repair, which makes it noteworthy in regards to treating and preventing cancer. Research suggests that people with varying forms of MC-1R could be more susceptible to basal cell and squamous cell carcinoma. There is optimism regarding the potential of the modified PT-141 in addressing challenges associated with these variants, providing potential pathways for preventing or treating these specific cancer types.

At present, PT-141 is receiving significant attention in regards to treating sexual dysfunction. The potential, however, goes beyond addressing sexuality and hemorrhage issues exclusively. MC-4R, being a target of PT-141, is linked to specific instances of obesity, potentially contributing to around 6% of cases of early-onset obesity. Studying PT-141’s influence on this particular cause of obesity could reveal potential intervention pathways. Aside from MC-4R, PT-141 also affects MC-1R, a receptor involved in pain, inflammation, kidney pathology and the spread of infection, opening up diverse avenues for research.

When administered subcutaneously in mice, PT-141 demonstrates excellent bioavailability and minimal side effects. It is of the utmost importance to adjust dosage considerations from mice to humans. PT-141 offered at Peptide Sciences is exclusively meant for educational and scientific research purposes. It is not appropriate for human consumption. Only licensed researchers should make purchases.

The above literature was researched, edited and organized by Dr. Logan, M.D. Dr. Logan holds a doctorate degree from Case Western Reserve University School of Medicine and a B.S. in molecular biology.

Dr. Sheryl A. Kingsberg is the chief of behavioral medicine at University Hospitals Case Medical Center and professor in Reproductive Biology and Psychiatry at Case Western Reserve University. Her areas of clinical specialization include sexual medicine, female sexual disorders, cognitive behavioral psychotherapy, menopause, pregnancy and postpartum mood disorders, psychological aspects of infertility, and psychological and sexual aspects of cancer. Dr. Kingsberg’s primary research interests are in treatments for female sexual disorders and the psychological aspects of infertility and menopause.

She led a randomized, placebo-controlled dose-finding trial for PT-141. She has numerous publications in many national and international journals, sits on the editorial board of Menopause and has authored numerous chapters on topics including perimenopause and sexuality, oocyte donation, infertility and aging, the treatment of psychogenic erectile dysfunction and sexuality after cancer.

Dr. Kingsberg received her PhD from the University of South Florida in Tampa and completed her fellowship in sexual medicine at University Hospitals Case Medical Center. She is an active member in a number of national and international organizations including the American Psychological Association and the American Society for Reproductive Medicine. She currently sits on the Board of Trustees of The North American Menopause Society, and serves as the current treasurer of the Society for Assisted Reproductive Technologies. Dr. Kingsberg s a past president of The International Society for the Study of Women’s Sexual Health.

Dr. Sheryl A. Kingsberg is being referenced as one of the leading scientists involved in the research and development of PT-141. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Peptide Sciences and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide. Dr. Kingsberg is listed in [12] under the referenced citations.

1. M. Sandrock, A. Schulz, C. Merkwitz, T. Schöneberg, K. Spanel-Borowski, and A. Ricken, “Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice,” Reprod. Biol. Endocrinol. RBE, vol. 7, p. 24, Mar. 2009.
2. R. C. Rosen, L. E. Diamond, D. C. Earle, A. M. Shadiack, and P. B. Molinoff, “Evaluation of the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in patients with an inadequate response to Viagra,” Int. J. Impot. Res., vol. 16, no. 2, pp. 135–142, Apr. 2004. [PubMed]
3. H. Wessells, V. J. Hruby, J. Hackett, G. Han, P. Balse-Srinivasan, and T. W. Vanderah, “Ac-Nle-c[Asp-His-DPhe-Arg-Trp-Lys]-NH2 induces penile erection via brain and spinal melanocortin receptors,” Neuroscience, vol. 118, no. 3, pp. 755–762, 2003. [PubMed]
4. A.-S. Rössler, J. G. Pfaus, H. K. Kia, J. Bernabé, L. Alexandre, and F. Giuliano, “The melanocortin agonist, melanotan II, enhances proceptive sexual behaviors in the female rat,” Pharmacol. Biochem. Behav., vol. 85, no. 3, pp. 514–521, Nov. 2006. [PubMed]
5. M. R. Safarinejad and S. Y. Hosseini, “Salvage of sildenafil failures with bremelanotide: a randomized, double-blind, placebo controlled study,” J. Urol., vol. 179, no. 3, pp. 1066–1071, Mar. 2008. [PubMed]
6. A. H. Clayton et al., “Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial,” Womens Health Lond. Engl., vol. 12, no. 3, pp. 325–337, 2016. [PubMed]
7. M. K. Miller, J. R. Smith, J. J. Norman, and A. H. Clayton, “Expert opinion on existing and developing drugs to treat female sexual dysfunction,” Expert Opin. Emerg. Drugs, vol. 23, no. 3, pp. 223–230, 2018. [PubMed]
8. “AMAG Pharmaceuticals and Palatin Technologies Enter Into Exclusive Licensing Agreement for North American Rights to RekyndaTM (bremelanotide), a Potential Treatment for a Common Female Sexual Disorder – AMAG Pharmaceuticals.” . [MarketWatch]
9. H. Ji et al., “The Synthetic Melanocortin (CKPV)2 Exerts Anti-Fungal and Anti-Inflammatory Effects against Candida albicans Vaginitis via Inducing Macrophage M2 Polarization,” PLoS ONE, vol. 8, no. 2, Feb. 2013. [PLOS ONE]
10. V. Maresca, E. Flori, and M. Picardo, “Skin phototype: a new perspective,” Pigment Cell Melanoma Res., vol. 28, no. 4, pp. 378–389, Jul. 2015. [PubMed]
11. L. Feller, R. a. G. Khammissa, B. Kramer, M. Altini, and J. Lemmer, “Basal cell carcinoma, squamous cell carcinoma and melanoma of the head and face,” Head Face Med., vol. 12, p. 11, Feb. 2016. [PubMed]
12. Clayton AH, Althof SE, Kingsberg S, et al. Bremelanotide for female sexual dysfunctions in premenopausal women: a randomized, placebo-controlled dose-finding trial. Womens Health (Lond). 2016;12(3):325–337. doi:10.2217/whe-2016-0018
13. T. R. McMillan, M. A. M. Forster, L. I. Short, A. P. Rudecki, D. L. Cline, and S. L. Gray, “Melanotan II, a melanocortin agonist, partially rescues the impaired thermogenic capacity of pituitary adenylate cyclase-activating polypeptide deficient mice,Exp. Physiol. , vol. 106, no. 2, pp. 427–437, Feb. 2021, doi: 10.1113/EP088838.”
14. C. Spana, R. Jordan, and S. Fischkoff, “Effect of bremelanotide on body weight of obese women: Data from two phase 1 randomized controlled trials,Diabetes Obes. Metab., vol. 24, no. 6, pp. 1084–1093, Jun. 2022, doi: 10.1111/dom.14672. ”

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The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body.  These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease.  Bodily introduction of any kind into humans or animals is strictly forbidden by law.