PT-141

The Libido Enhancer

Boost Your Libido: Experience the Benefits of PT-141

PT-141, also known as Bremelanotide, is a synthetic peptide used for its potential effects on sexual dysfunction. It originally stems from the peptide hormone Melanotan 2, which was developed to promote skin tanning. Researchers discovered that a particular fragment of Melanotan 2, now known as PT-141, has effects that could enhance sexual arousal.

PT-141 works differently from other traditional treatments for sexual dysfunction, such as Viagra. Rather than acting on the vascular system, PT-141 targets the nervous system. It does this by activating the melanocortin receptors, which are involved in various physiological functions including skin pigmentation, inflammation, energy homeostasis, and the regulation of sexual behavior. Specifically, PT-141 binds to the melanocortin 4 receptor, which is important for inducing erections and sexual desire.

Potential Benefits Under Research

• Treatment of Erectile Dysfunction: It could serve as an alternative treatment for erectile dysfunction, particularly for those unresponsive to traditional medications.
• Treatment of Female Sexual Arousal Disorder: The peptide is being researched as a treatment for female sexual arousal disorder, offering a new option for women.
• Non-Vascular Approach: PT-141 acts via the central nervous system, potentially minimizing vascular-related side effects, differing from other sexual dysfunction treatments.
• Rapid Onset of Action: Early results suggest PT-141 may work relatively quickly, suitable for spontaneous sexual activity.
• Reduction of Hemorrhage: There is exploratory research into PT-141’s potential to help manage and reduce hemorrhage, although this is less documented and understood.
• Potential Anti-Inflammatory Effects: Some studies have hinted at PT-141’s capabilities in modulating inflammation, which might be beneficial in various infectious or autoimmune diseases.
• Cancer Research: Early-stage research is investigating whether PT-141’s interaction with melanocortin pathways might influence tumor growth or cancer treatment, particularly in cancers influenced by these pathways.

Dosing Protocol for Research Purposes

General Use:

• Dosage: 1.75 mg
• Administration: Subcutaneous injection
• Timing: Administered as needed, at least 45 minutes before anticipated sexual activity.
• Maximum Frequency: Should not be used more than once in 24 hours, and not more than eight times per month.

Clinical Study Dosages:

1. Hypoactive Sexual Desire Disorder in Premenopausal Women:
   • Dosage: 1.75 mg
   • Administration: Subcutaneous injection
   • Timing: Administered as needed, at least 45 minutes before anticipated sexual activity.
   • Study Results: Demonstrated efficacy in increasing sexual desire and reducing distress associated with low sexual desire.
2. FDA Approval and Guidelines:
   • Dosage: 1.75 mg
   • Administration: Subcutaneous injection
   • Timing: Administered as needed, at least 45 minutes before anticipated sexual activity.
   • Maximum Frequency: Should not be used more than once in 24 hours, and not more than eight times per month.

Overview

PT-141, also called bremelanotide, is sometimes referred to as the female Viagra because the peptide was previously investigated in phase llb human clinical trials for use in treating female hypoactive sexual desire disorder (HSDD). PT-141 is a melanocortin that binds primarily to melanocortin 4 receptor (MC-4R) and MC-lR. In 2009, PT-141 was also investigated as a treatment for acute hemorrhage. PT-141 is a derivative of another synthetic melanocortin, melanotan 2 (MT-2).

Structure

Sequence: Ac-Nle-Asp(l)-His-D-Phe-Arg-Trp­Lys(l)
Molecular Formula: C50H6aN14O10
Molecular Weight: 1025.182 g/mol
PubChem CID: 9941379
CAS Number: 189691-06-3

PT-141 Research

PT-141 and Sexual Arousal

PT-141 is a unique peptide in that it stimulates the MC-4R, which is known to produce sexual arousal in the central nervous system and influence sexual behavior. Studies in mice have shown that agonist binding to MC-4R causes sexual arousal and increased copulation in both males and females. Because PT-141 works via a different mechanism than drugs like Viagra, it is possible to treat sexual arousal disorders in both men and women that stem from causes other than reduced blood flow to the genitals.

A study of men with erectile dysfunction (ED) who did not respond to sildenafil (Viagra) found that roughly one-third experienced adequate erection for sexual intercourse with PT-141 (administered via nasal spray). There was also a strong dose-­dependent response in the trial, indicating that PT-141 is indeed effective in certain cases. This suggests that PT-141 could offer insight into correcting ED in settings where sildenafil has failed and may offer insight into central causes of hypoactive sexual desire.

Interestingly, PT-141 was pulled from clinical trials before it reached approval for use in women suffering from HSDD. This is despite signs that the drug increased the number of satisfying sexual events per month and decreased female sexual distress scores in a statistically significant manner without any substantial side effects. Many experts who treat female sexual dysfunction (FSD) were dismayed to find the peptide was not being advanced despite positive results. They point to a lack of established endpoints for trials of FSD and socio-cultural biases against women’s sexual health as the primary roadblocks that are inhibiting approval of what they see as much-needed therapies. They hope that greater attention will be given to the topic and that the FDA will establish more concrete guidelines for evaluating therapies like PT-141 that can offer benefits. These experts also expressed dismay that the pharmacological treatments were not tested in conjunction with other established means of treating sexual dysfunction as they believe that the combination may prove synergistic and that peptides like PT-141 may be useful for overcoming initial barriers and jump-starting psychological treatment modalities.

In 2017, partly in response to the outcry against the cessation of earlier trials, Phase II Reconnect trials were launched using subcutaneous injections of PT-141 for FSD. The newest version of PT-141, called Rekynda, may soon be available for use in the United States. It would be legal to use PT-141 off­ label, at that point, to treat both male and female sexual dysfunction. These new trials have relied on the kind of modified endpoints that experts in FSD have touted as beneficial to seeing these kinds of treatments approved.

PT-141 and Hemorrhage

In 2009, PT-141 was modified slightly 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 the setting of hypovolemic (hemorrhagic) shock. The drug, when administered intravenously, does not produce substantial side effects. It was last in phase llb trials. The modified version of PT-141 is referred to as PL-6983.
PT-141 and Infection

The MC-1R has been found, in a rat model of a specific fungal infection, to possess important anti­fungal and anti-inflammatory properties. This is of particular importance because current antifungals are limited in terms of their mechanism of action and all produce serious and treatment-limiting side effects in certain patients. Having an alternative to use in the treatment of fungal infections could reduce morbidity and mortality substantially, especially in patients with immune compromise.

PT-141 and Cancer

The MC-1R receptor is an important stimulus of DNA repair pathways and thus is of interest in cancer treatment and prevention. Research shows that people with variants of MC-1R are at increased risk for both basal cell and squamous cell carcinoma. Altered PT-141 may be able to correct the problems experienced as a result of these variants and prevent or treat these cancers.

Research Directions

Right now, PT-141 has received widespread and intense attention as a treatment for sexual dysfunction. There is, however, a great deal of potential research outside of sexual dysfunction and hemorrhage that PT-141 could be applied to. For instance, MC-4R is well-known to be defective or missing in certain cases of obesity and may account for as much as 6% of all cases of early-onset obesity. PT-141 offers a unique means of exploring this particular cause of obesity and potentially illustrating a pathway for intervention. MC-lR plays roles in both pain and inflammation as well as kidney pathology and the spread of infection. There is a plethora of available research that PT-141 could help to shed light on.

PT-141 exhibits minimal side effects, low oral and excellent subcutaneous bioavailability in mice. Per kg dosage in mice does not scale to humans. 

Dosage

• 2 mg injected subcutaneously around 1 hour before sex, with only one injection every 72 hours.

Article Author

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.

Scientific Journal Author

Dr. Sheryl A. Kingsberg is the chief of behavioral medicine at University Hospitals Case Medical Center and a 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 is 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 Guide to Peptide 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 under the referenced citations.

Referenced Citations

1. M. Sandrock, A. Schulz, C. Merkwitz, T. Schoneberg, K. SRanel-Borowski, and A. Ricken, “Reduction in corpora lutea number in obese melanocortin-4-receptor-deficient mice,” Reprod. Biol. Endocrinol. RBE, vol. 7, R· 24, Mar. 2009. 
2. R. C. Rosen, L. E. Diamond, D. C. Earle, A. M. Shadiack. and P. B. Molinoff. “Evaluation of the safely pharmacokinetics and pharmacodynamic effects of subcutaneous administered PT-141, a melanocortin receptor agonist in healthy. male subjects and in patients with an inadequate response to Viagra,” Int. J. lmport. Res., vol. 16, no. 2, RP-:. 135-142, A12r. 2004. [PubMed]
3. H. Wessells, V. J. Hruby, J. Hackett. G. Han, P. Baise-Srinivasan. and T. W. Vanderah, “Ac­nce-c[As12-His-DPhe-Arg-Tr12-Lys]-NH2 induced penile erection via brain and spinal melanocortin receptors,” Neuroscience, vol. 118, no. 3, 1212. 755-762, 2003. [PubMed] 
4. A.-S. Rossler, J. G. Pfaus, H. K. Kia, J. Bernabe, L. Alexandre, and F. Giuliano, “The melanocortin agonist melanotan II, enhances proceptive sexual behaviors in the female rat.” Pharmacol. Biochem. Behav.1 vol. 85, no.
   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. Ural., vol. 179, no. 3, 1212. 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 Land. Engl., vol. 12, no. 3, 1212. 325-337, 2016.
   [PubMed]
7. M. K. Miller. J. R. Smith, J. J. Norman, and A. H. ClayJon, “Expert opinion on existing and developing drugs to treat female sexual dysfunction,” Expert Opin. Emerg. Drugs, vol. 23, no. 3, QR- 223-230, 2018. [PubMed] 
8. “AMAG Pharmaceuticals and Palatin Technologies Enter Into Exclusive Licensing Agreement for North American Rights to Renda TM (bremelanotide), a Potential Treatment for a Common Female Sexual Disorder -AMAG Pharmaceuticals.
9. H. Ji et al., “The Synthetic Melanocortin
   .(CKPV)2 Exerts Anti-Fungal and Anti­inflammatory.’. Effects against Candida albicans Vaginitis via Inducing Macrophage M2 Polarization,” PLoS ONE, vol. 81 no. 2, Feb. 2013. [PLOS ONE]
10. V. Maresca, E. Flori, and M. Picardo, “Skin pototype: a new perspective,” Pigment Cell Melanoma Res., vol. 28, no. 4, RR- 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, R· 11, Feb. 2016. [PubMed] 
12. Clayjon AH, Althof SE, Kingsberg S, et al. Bremelanotide for female sexual dysfunctions in Premenopausal women: a randomized, placebo-controlled dose-finding trial. Womens Health (LondJ 2016;12rn):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..1 “Melanotan II, a melanocortin agonist. partially. rescues the impaired thermogenic capacity. of pituitary adenylate cyclase­-activating_polypeptide deficient mice.Exp:. Phvsiol. , 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. 61 RR- 1084-1093. Jun. 2022. doi: 10.1111/dom.14672. “