PT-141

PT-141 Peptide

PT-141 (Bremelanotide) is a synthetic cyclic heptapeptide structurally connected to α-melanocyte-stimulating hormone (α-MSH). It operates as a melanocortin receptor agonist, demonstrating activity primarily at MC3R and MC4R receptors. Research on PT-141 focuses on its influence on sexual behavior, central nervous system (CNS) signaling, and melanocortin pathway modulation.

Unlike earlier compounds derived from the melanocortin family, PT-141 demonstrates minimal activity at the MC1R receptor, which is the subtype associated with skin pigmentation. This selective receptor profile makes PT-141 a unique experimental agent for investigating central melanocortin mechanisms without affecting pigmentation processes.

PT-141 Peptide General Information

PT-141 was created through structural refinement of the α-MSH analogue Melanotan II, designed to enhance its selectivity and potency toward central melanocortin receptors associated with sexual function and energy regulation. Experimental data indicate PT-141 influences hypothalamic neuronal activity, modulating sexual behavior, arousal mechanisms, and appetite control.

Preclinical investigations have explored PT-141's effects in models of sexual dysfunction, metabolic balance, and neuroendocrine signaling, highlighting its significance as a research compound for studying central melanocortin pathways and their roles in neural and behavioral regulation.

PT-141 Peptide Structure

PT-141 Peptide Research Data

Melanocortin System and Sexual Function

Preclinical studies demonstrate that PT-141 activates MC3R and MC4R receptors within the hypothalamus, promoting sexual arousal and copulatory behavior in both male and female experimental models. Unlike phosphodiesterase type 5 inhibitors (PDE5i), PT-141 primarily acts on central neural pathways rather than peripheral mechanisms, making it a valuable experimental agent for investigating neuroendocrine regulation of sexual function.

Neuroendocrine and Appetite Regulation

The melanocortin signaling network plays a crucial role in maintaining energy balance and appetite control. Research involving PT-141 has explored its effects on food intake suppression and weight regulation in rodent models, underscoring its relevance in studies of metabolic and neuroendocrine processes.

CNS Pharmacology and Safety

PT-141 exhibits effective blood–brain barrier permeability and receptor selectivity, prompting scientific interest in its potential use in neuroendocrine and metabolic investigations. Preliminary safety evaluations indicate a favorable pharmacological profile when administered intranasally or subcutaneously under controlled experimental conditions.

Additional Research Applications

Further exploratory research has examined PT-141's potential in ischemic protection, neuroinflammatory modulation, and behavioral neuroscience. These findings position PT-141 as a versatile tool compound for advancing research into melanocortin receptor biology and related central nervous system mechanisms.

PT-141 and Sexual Arousal

PT-141 is a specialized peptide known for its ability to activate the MC4R receptor, which plays a key role in regulating sexual arousal and behavior through central nervous system pathways. Experimental research in animal models has demonstrated that agonist activity at MC4R receptors stimulates sexual motivation and copulatory behavior in both male and female subjects.

Unlike medications such as sildenafil (Viagra) that act by increasing blood flow, PT-141 operates through a distinct neurochemical mechanism, targeting central arousal pathways. This makes it a promising compound for studying and potentially addressing sexual arousal disorders in both men and women that originate from neurological rather than vascular causes.

Clinical research involving men with erectile dysfunction (ED) unresponsive to sildenafil treatment found that approximately one-third achieved satisfactory sexual performance following intranasal administration of PT-141. The study also observed a dose-dependent effect, supporting the compound's efficacy in select cases. These findings suggest that PT-141 may provide valuable insights into treating ED associated with central nervous system factors and may contribute to understanding the neurobiological basis of low sexual desire.

PT-141 and Hemorrhage

In 2009, researchers developed a slightly modified version of PT-141 to explore its therapeutic potential for hemorrhagic shock. Because PT-141 acts as an agonist at both the MC1R and MC4R receptors, it has demonstrated the ability to reduce ischemia and protect tissues from oxygen deprivation under conditions of severe blood loss (hypovolemic shock). When administered intravenously, PT-141 did not exhibit major adverse effects. The modified compound, known as PL-6983, advanced through phase IIb clinical trials, showing encouraging protective effects without significant toxicity.

PT-141 and Infection

Experimental studies using rat models of fungal infection revealed that activation of the MC1R receptor by PT-141 can elicit notable antifungal and anti-inflammatory actions. This finding is highly relevant given that existing antifungal medications are constrained by limited mechanisms of action and often produce serious side effects that restrict their long-term use. PT-141's unique receptor-mediated activity positions it as a potential alternative therapeutic approach for fungal infections, particularly in immunocompromised patients, where reducing inflammation and infection-related mortality is of critical importance.

Article Author

This literature review was prepared, compiled, and edited by Dr. Roger T. Dorr, Ph.D. Dr. Dorr is an accomplished pharmacologist and melanoma specialist recognized for his pioneering research on melanocortin receptor agonists, including the development of PT-141 (Bremelanotide). His groundbreaking work at the University of Arizona has significantly advanced scientific understanding of the melanocortin system, particularly its involvement in skin pigmentation, sexual function, and energy homeostasis. Through his extensive research, Dr. Dorr has played a pivotal role in the advancement of synthetic α-MSH analogues and in uncovering their therapeutic potential across dermatological, endocrine, and neurobiological applications.

Scientific Publication Author

Dr. Roger T. Dorr has authored and co-authored numerous influential studies exploring melanocortin receptor signaling and peptide analog pharmacology. Collaborating with leading figures such as M.E. Hadley, J.E.S. Wikberg, F. Giuliano, and L.H. van der Ploeg, he has contributed to elucidating the distinct functions of melanocortin receptor subtypes (MC1R–MC5R) and their regulatory roles in sexual behavior, metabolism, and neuroendocrine activity. The collective body of work from these researchers has been foundational in expanding knowledge of central melanocortin mechanisms and their implications for conditions involving sexual dysfunction, metabolic imbalance, and neural protection.

This acknowledgment serves solely to recognize the scientific contributions of Dr. Dorr and his collaborators. It does not imply endorsement, promotion, or affiliation. Montreal Peptides Canada maintains no professional, financial, or institutional association with Dr. Dorr or any researchers referenced herein.

Reference Citations

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Shadiack AM, et al. Melanocortin receptor agonists in sexual behavior research. Brain Res. 2007;1124(1):166–175.

Hadley ME, et al. Discovery and development of melanocortin receptor ligands. Ann N Y Acad Sci. 2006;994:1-15.

King SH, et al. PT-141: novel melanocortin analog in sexual arousal studies. J Sex Med. 2008;5(8):1939-1948.

Giuliano F, et al. Central melanocortin pathways and erectile function. Int J Impot Res. 2007;19(1):17–23.

Clayton AH, et al. Bremelanotide in female sexual dysfunction studies. J Sex Med. 2016;13(5):696-706.

Wessells H, et al. Central melanocortin modulation of sexual function in humans. J Urol. 2000;164(3 Pt 1):738-743.

van der Ploeg LH, et al. Melanocortin receptors and obesity research. Endocr Rev. 2002;23(6):728-743.

Kask A, et al. Melanocortins in the brain: from pigmentation to appetite. Eur J Pharmacol. 1999;375(1-3):1–12.

Wikberg JES, et al. Five subtypes of melanocortin receptors in energy homeostasis. Peptides. 1999;20(4):401-410.