PT-141

PT-141

PT-141 (Bremelanotide) is a cyclic heptapeptide analogue of α-MSH derived from Melanotan-II via removal of the C-terminal amide. In preclinical research it has been studied as a non-selective melanocortin receptor agonist with primary activity at MC3R and MC4R, investigated for central nervous system melanocortin pathway signaling, neurogenic pathway modeling, and downstream hypothalamic response research.

Overview

Studies have suggested that PT-141 shows agonistic properties towards melanocortin receptors, namely MC3R and MC4R, which may result in elevated reactions in the central nervous system. MC3R, which appears to be primarily expressed in the brain, especially within the hypothalamus, might play a role in energy homeostasis. It has been hypothesized by research teams examining melanocortin receptor activity, that MC3R may potentially modulate the actions of other melanocortin receptors in this area. Moreover, MC3R might influence feeding behavior, possibly impacting appetite and food intake, and is thought to be involved in various metabolic processes, including the potential regulation of glucose and lipid metabolism.⁽³⁾ On the other hand, MC4R is believed to be essential in appetite control. When activated in the brain, it is considered to contribute to appetite regulation. MC4R is also posited to have a role in energy expenditure, with its activation possibly leading to an increase in energy output, which could contribute to weight reduction. This receptor has also been tentatively linked to reproductive function, especially in the potential regulation of the function of penile tissues and overall reproductive behavior.⁽⁴⁾ In publically available study, it was suggested by researchers that following binding with MC3R and MC4R receptors, the peptide appeared to lead to the activation of the neurons found in the hypothalamus, leading to apparently increased immunoreactivity.²⁽⁾ Neurons in the surrounding region of the central nervous system may also be stimulated as they intake the chemicals which then reportedly lead to sexual arousal in murine models.

PT-141 Chemical Makeup

Molecular formula: C₅₀H₆₈N₁₄O₁₀
Molecular weight: 1025.18 g/mol
Other Known Titles: Bremelanotide

Research and Clinical Studies

PT-141 Peptide Initial Studies

This early 2000 study was conducted to understand the potential of PT-141 peptide in murine models. The murine models were used as the subject in this study to determine how the peptide may impact their sexual behavior.⁽⁵⁾ After presentation, it was reported that the female rats appeared to exhibit elevated sexual desire without any increase/decrease in the sexual pace, lumbar lordosis, or any other sexually-related behaviors. After analysis, it was suggested by the researchers that the peptide did not directly impact a generalized motor activation, instead it may have potential selective pharmacological impact that may stimulate the central nervous system, mainly the melanocortin receptor activities, which might result in elevated sexual arousal. More specifically, the researchers commented that “ The ability of PT-141 to enhance solicitation in two distinctive testing environments indicates that the effect is selective and stable, and suggests that central melanocortin systems are part of the neurochemical network that evokes appetitive sexual behavior in female rats.”⁽⁵⁾

PT-141 Peptide and Arousal

The potential activation of the MC4R by PT-141 may also upregulate the production of vasodilators like nitric oxide (NO) in penile tissues, leading to improved erection potential, as suggested by research.⁽⁶⁾ The peptide is posited to be a metabolite of Melanotan-2 (MT-II), and both appear to activate the same receptors. For example, it has been posited that melanocortin agonists might lead to concentration-related increases in cavernosal pressure. SHU 9119, an agent that is possibly a non-selective antagonist of MC3R and MC4R, appears not to have had a significant impact on cavernosal or systemic blood pressure. However, it seems to have negated the increases in cavernosal pressure that melanocortin agonists potentially induced. This same agent, SHU 9119, also appears to have inhibited the depressor response that was probably produced by melanocortin agonists. Moreover, when a combination containing phentolamine mesylate, papaverine, and PGE1 was introduced directly into the cavernosal tissue, it reportedly led to a 4-fold increase in cavernosal pressure. The study also hypothesized the role of the NO-cyclic GMP-dependent pathway in relation to the melanocortin agonists-induced increases in cavernosal pressure. This was done by performing a bilateral transection of the pudendal nerves and inhibiting NO synthase using L-NAME. The results indicate that either removing the pudendal nerves or pretreating with L-NAME may negate the increases in intracavernosal pressure that melanocortin agonists likely induced in the anesthetized murine models. From the gathered data, it was tentatively inferred that the activation of central melanocortin receptors by melanocortin agonists might lead to an increase in cavernosal pressure, probably achieved through the neuronal release of NO.⁽⁶⁾