PT-141 Peptide

Bremelanotide, also known as PT-141, is a cyclic synthetic peptide composed of seven amino acids.(1) It is classified as a melanocortin receptor agonist, exhibiting activity similar to the naturally occurring hormone alpha-melanocyte-stimulating hormone (α-MSH).(2) Bremelanotide is derived as a metabolite of another synthetic analogue, Melanotan II.

Early research into melanocortin hormones suggested that they may play roles in regulating a variety of physiological processes. In experimental models, administration of these hormones was associated with increased reproductive activity, which has since become a primary focus of ongoing research into the PT-141 peptide.

Overview

Studies have suggested that PT-141 (Bremelanotide) exhibits agonistic activity at melanocortin receptors, particularly MC3R and MC4R, which may contribute to its effects within the central nervous system. MC3R is primarily expressed in the brain, especially in the hypothalamus, and is thought to play a role in energy homeostasis. Researchers have proposed that MC3R may help modulate the activity of other melanocortin receptors in this region and may influence feeding behaviour, appetite regulation, and broader metabolic processes such as glucose and lipid metabolism.(3)

MC4R, on the other hand, is considered a key receptor in appetite regulation. Its activation within the brain is associated with control of food intake and may also influence energy expenditure, potentially increasing metabolic output. In addition, MC4R has been linked to reproductive function, with research suggesting a role in regulating sexual behaviour and physiological responses related to reproductive tissues.(4)

Experimental findings have indicated that binding of PT-141 to MC3R and MC4R may lead to activation of hypothalamic neurons, resulting in increased neural activity within these regions. This activation may extend to surrounding areas of the central nervous system, where downstream signalling has been associated with behavioural responses such as sexual arousal in murine models.

PT-141 Chemical Makeup
  • Molecular formula: C50H68N14O10
  • Molecular weight: 1025.18 g/mol
  • Other Known Titles: Bremelanotid
Research and Clinical Studies
PT-141 Peptide Initial Studies

An early 2000s study(5) investigated the potential effects of PT-141 (Bremelanotide) on sexual behaviour in murine models, specifically focusing on female rats. Following administration of the peptide, researchers observed an apparent increase in sexual motivation or desire. Notably, this increase did not coincide with changes in other behavioural parameters such as sexual pace, lumbar lordosis, or general motor activity.

Based on these findings, the researchers suggested that PT-141 did not induce a broad activation of motor function, but rather exerted a more selective pharmacological effect on the central nervous system. This effect was proposed to be mediated through melanocortin receptor activity, particularly within neural circuits associated with sexual behaviour.

The authors concluded that the peptide appeared to enhance sexual solicitation in a consistent and selective manner across different testing environments, indicating that central melanocortin systems may form part of the neurochemical network involved in regulating appetitive sexual behaviour in female rats.(5)

PT-141 Peptide and Arousal

Activation of melanocortin-4 receptors (MC4R) by PT-141 has been proposed to influence erectile function through central and peripheral mechanisms. Research suggests that this activation may upregulate the production of vasodilators such as nitric oxide (NO) within penile tissue, potentially contributing to improved erectile response.(6)

PT-141 is considered a metabolite of Melanotan II (MT-II), and both compounds appear to act on similar melanocortin receptors. Experimental findings have indicated that melanocortin receptor agonists may produce dose-dependent increases in cavernosal pressure, a key physiological marker associated with erection. In contrast, SHU-9119—a non-selective antagonist of MC3R and MC4R—did not significantly alter baseline blood pressure but appeared to block the increases in cavernosal pressure induced by melanocortin agonists, suggesting receptor-specific involvement.

Further investigations explored the role of the nitric oxide–cyclic GMP (NO–cGMP) pathway. When researchers disrupted neural input by transecting the pudendal nerves or inhibited nitric oxide synthase using L-NAME, the increases in intracavernosal pressure were largely abolished. These findings suggest that the effects of melanocortin agonists like PT-141 may depend on intact neural pathways and NO signalling.

Additionally, direct administration of vasodilatory agents such as phentolamine, papaverine, and prostaglandin E1 (PGE1) into cavernosal tissue resulted in a significant increase in cavernosal pressure, supporting the role of vascular mechanisms in erectile function. Overall, the data suggest that activation of central melanocortin receptors may enhance erectile responses through neuronal signalling pathways that involve nitric oxide release, although these mechanisms remain under investigation.(6)

PT-141 Peptide and the Central Nervous System

Studies investigating PT-141 (Bremelanotide) have explored its potential effects within the central nervous system (CNS), particularly in brain regions associated with sexual behaviour.(7) In murine models with elevated levels of female reproductive hormones, researchers examined both appetitive behaviours (such as increased solicitation and agitation) and consummatory behaviours (such as lordosis). Following administration of the peptide, results indicated an increase in appetitive sexual behaviours without significant changes in sexual pace or lordosis.

These effects were observed following both peripheral administration and direct delivery into brain regions such as the lateral ventricles and the medial preoptic area (mPOA), though not in the ventromedial hypothalamus. The mPOA is considered a key region involved in regulating sexual motivation across species. PT-141 appeared to activate this region, along with other hypothalamic and limbic structures linked to sexual behaviour. Researchers hypothesised that this effect may involve activation of dopaminergic pathways within the mPOA, although further investigation is required to confirm this mechanism. The peptide was described as having the behavioural, pharmacological, and neuroanatomical specificity required to potentially influence sexual function.(7)

To further explore these mechanisms in humans, a randomized, double-blind, placebo-controlled crossover study was conducted using psychometric assessments, functional neuroimaging, and hormonal analysis.(8) The findings suggested that melanocortin-4 receptor (MC4R) agonists such as PT-141 may increase sexual desire for up to 24 hours compared to placebo. Neuroimaging data indicated increased activity in regions such as the cerebellum and supplementary motor areas, alongside decreased activity in the secondary somatosensory cortex when subjects were exposed to erotic stimuli. Additionally, enhanced functional connectivity between the amygdala and insula was observed, suggesting altered processing of sexual stimuli.

Collectively, these findings support the hypothesis that MC4R agonists like PT-141 may modulate sexual behaviour through central neural pathways, particularly by influencing brain regions involved in motivation, emotion, and sensory processing, although the precise mechanisms remain under ongoing investigation.

PT-141 peptide is available for research and laboratory purposes only. Please speak to our friendly research team to find out more and for sourcing options.

References:

  1. Pfaus, J., Giuliano, F., & Gelez, H. (2007). Bremelanotide: an overview of preclinical CNS effects on female sexual function. The journal of sexual medicine, 4 Suppl 4, 269–279.    https://doi.org/10.1111/j.1743-6109.2007.00610.x

  2. National Center for Biotechnology Information (2023). PubChem Compound Summary for CID 9941379, Bremelanotide. Retrieved August 10, 2023 from   https://pubchem.ncbi.nlm.nih.gov/compound/Bremelanotide.

  3. Molinoff, P. B., Shadiack, A. M., Earle, D., Diamond, L. E., & Quon, C. Y. (2003). PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Annals of the New York Academy of Sciences, 994, 96–102.   https://doi.org/10.1111/j.1749-6632.2003.tb03167.x

  4. Renquist, B. J., Lippert, R. N., Sebag, J. A., Ellacott, K. L., & Cone, R. D. (2011). Physiological roles of the melanocortin MC₃ receptor. European journal of pharmacology, 660(1), 13–20.   https://doi.org/10.1016/j.ejphar.2010.12.025

  5. Adan, R. A., Tiesjema, B., Hillebrand, J. J., la Fleur, S. E., Kas, M. J., & de Krom, M. (2006). The MC4 receptor and control of appetite. British journal of pharmacology, 149(7), 815–827.   https://doi.org/10.1038/sj.bjp.0706929

  6. Pfaus, J. G., Shadiack, A., Van Soest, T., Tse, M., & Molinoff, P. (2004). Selective facilitation of sexual solicitation in the female rat by a melanocortin receptor agonist. Proceedings of the National Academy of Sciences of the United States of America, 101(27), 10201–10204.   https://doi.org/10.1073/pnas.0400491101

  7. Vemulapalli, R., Kurowski, S., Salisbury, B., Parker, E., & Davis, H. (2001). Activation of central melanocortin receptors by MT-II increases cavernosal pressure in rabbits by the neuronal release of NO. British journal of pharmacology, 134(8), 1705–1710.   https://doi.org/10.1038/sj.bjp.0704437

  8. Thurston, L., Hunjan, T., Mills, E. G., Wall, M. B., Ertl, N., Phylactou, M., Muzi, B., Patel, B., Alexander, E. C., Suladze, S., Modi, M., Eng, P. C., Bassett, P. A., Abbara, A., Goldmeier, D., Comninos, A. N., & Dhillo, W. S. (2022). Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder. The Journal of clinical investigation, 132(19), e152341.   https://doi.org/10.1172/JCI152341

Dr. Marinov

Dr. Marinov (MD, Ph.D.) is a researcher and chief assistant professor in Preventative Medicine & Public Health. Prior to his professorship, Dr. Marinov practiced preventative, evidence-based medicine with an emphasis on Nutrition and Dietetics. He is widely published in international peer-reviewed scientific journals and specializes in peptide therapy research.

PT-141 Peptide