Everything below concerns Agonist. We keep the language plain, cite what the science says, and separate well-supported claims from open questions.
Last reviewed on 2025-12-28. Where a claim depends on a specific study, the study is described rather than over-claimed.
Bremelanotide is a synthetic cyclic heptapeptide developed as an analogue of alpha-melanocyte-stimulating hormone, a naturally occurring peptide involved in pigmentation and appetite signalling. Its structure contains seven amino acid residues joined by a lactam bridge that closes the ring between two side chains. The molecular formula is C50H68N14O10 and the nominal molecular mass is near 1025 daltons. Much of the early laboratory literature refers to the same molecule by the development code PT-141.
The compound emerged from a research programme examining melanocortin analogues for effects on skin pigmentation. During early human studies, participants reported spontaneous erections as an unexpected side effect, which redirected development toward sexual function rather than tanning. An intranasal formulation was investigated in clinical trials but did not reach market approval. A subcutaneous injectable version later completed the regulatory process, and the nasal route does not appear in approved labelling.
Approved use is narrow and jurisdiction-specific. In the United States, the injectable product is authorised for premenopausal women with acquired, generalised hypoactive sexual desire disorder, a diagnosis that requires documented distress. It is not approved for men, for postmenopausal women, or for use alongside hormonal contraceptives under the approved labelling. Outside regulated markets, the same peptide is frequently sold as a research chemical, where identity, purity, and sterility are not independently verified.
The lyophilised solid is relatively stable when kept dry, protected from light and held at reduced temperature, commonly minus 20 degrees Celsius or lower for long-term storage. In solution the peptide is more vulnerable: tryptophan oxidation, hydrolysis of the lactam bridge and aggregation all become relevant over time, and the rate depends on pH, buffer composition and concentration. Repeated freeze-thaw cycles are generally avoided because they promote aggregation. Aqueous working solutions are typically prepared fresh or split into single-use aliquots to limit degradation before analysis.
Published studies differ in design, population and endpoint definition, so results are not always directly comparable across reports. Some trials used patient-reported measures of desire and distress, while others tracked physiological or behavioural outcomes. Questions that remain open include the durability of effects beyond short follow-up periods, the frequency of transient blood pressure elevation observed after administration, and whether a subtype-selective analogue could separate central effects from pigmentation-related activity. These points are usually framed as unresolved rather than settled in review literature.
Routine characterisation of bremelanotide relies on reversed-phase high-performance liquid chromatography with ultraviolet detection near 214 nm, where the peptide backbone absorbs. Mass spectrometry, typically in tandem mode with electrospray ionisation, confirms identity and supports quantification in biological matrices. Additional checks include amino acid analysis, peptide mapping after enzymatic digestion, and confirmation of the lactam bridge, since incomplete cyclisation produces a mass-shifted by-product. Purity values above 95 percent are common in reference-grade material, though reports vary in how strictly related substances are resolved from the parent peak.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C50H68N14O10 | Cyclic heptapeptide backbone |
| Molecular mass | Approximately 1025 Da | Nominal mass of the free peptide |
| Appearance | White to off-white lyophilised powder | Typical for purified synthetic peptides |
| Solubility class | Freely soluble in water | Organic solubility is limited |
| Typical storage temperature | −20 °C or below | Protect from moisture and light |
Clinical research typically uses randomised, double-blind, placebo-controlled designs. The most common primary endpoint is the desire domain score of the Female Sexual Function Index, sometimes paired with a distress measure. Secondary outcomes include arousal, satisfaction, and event-based counts of satisfying sexual episodes. Across trials, average improvements are modest and individual responses vary widely. Whether benefits persist beyond a few months, and whether they depend on baseline hormone status, remain open questions rather than settled findings.
Melanocortin receptors form a family of five G-protein-coupled receptors designated MC1 through MC5. Bremelanotide binds most strongly at MC4R and MC1R, with weaker activity reported at MC3R and MC5R. MC4R is expressed in hypothalamic nuclei that coordinate energy balance and aspects of sexual behaviour. The prevailing interpretation is that central MC4R activation, rather than peripheral vascular effects alone, drives the reported changes in desire. This account remains partly inferential, since direct receptor-level measurement in living humans is not practical.
After subcutaneous administration, plasma concentrations rise within roughly thirty minutes and the elimination half-life is short, on the order of two to three hours. Reported physiological responses include transient increases in blood pressure and nausea, which tended to diminish with repeated dosing in trial settings. Because the peptide clears quickly, effects are not expected to persist long after a dose. Absorption from non-injected routes is poorly characterised, and nasal delivery produced variable plasma levels in older work.
Whether the behavioral effect originates centrally, peripherally, or through both remains an active question. Animal experiments using receptor antagonists and site-specific injections point toward hypothalamic melanocortin circuits as a key locus, but translating those findings to humans is not straightforward. Blood pressure changes observed in trials suggest a vascular component that may be peripherally mediated. The relationship between receptor occupancy and reported effect has not been mapped in humans, and no validated biomarker predicts response. This gap makes it difficult to explain individual variability on pharmacological grounds alone.
Bremelanotide acts as an agonist at melanocortin receptors, a family of five G-protein-coupled receptors labeled MC1 through MC5. Binding studies indicate activity at several of these subtypes rather than strict selectivity for one. Signalling proceeds mainly through Gs-mediated activation of adenylyl cyclase, raising intracellular cyclic AMP. The MC4 receptor, expressed in hypothalamic and limbic circuits, is widely regarded as the subtype most relevant to sexual response. Because the molecule is not subtype-selective, effects at other melanocortin receptors are expected and are used to explain some observed side effects.
=== Video games === The Persona series of games is heavily based on Jung's theories, representing the shadow, the persona, and archetype. The Nights into Dreams series of games is heavily based on Jung's theories. Jungian concepts are present in the Xeno series, including Xenogears; its reimagination as the Xenosaga trilogy; and a graphic novel, Perfect Works, published by the game's creator. The game Control is heavily influenced by Carl Jung's ideas, particularly synchronicity and shadow selves. Alan Wake takes inspiration from Carl Jung's ideas of archetype and individuation.
Kimchi is made of various vegetables and contains a high concentration of dietary fiber, while being low in food energy. The vegetables used in kimchi also contribute to intake of vitamin A, thiamine (B1), riboflavin (B2), calcium, and iron.
At a time of increasing cooperation between the Western Allies and the Soviet Union in the wake of the Nazi invasion of 1941, the influence of the Polish government-in-exile was seriously diminished by the death of Prime Minister Władysław Sikorski, its most capable leader, in a plane crash on 4 July 1943. Around that time, Polish-communist civilian and military organizations opposed to the government, led by Wanda Wasilewska and supported by Stalin, were formed in the Soviet Union. In July 1944, the Soviet Red Army and Soviet-controlled Polish People's Army entered the territory of future postwar Poland. In protracted fighting in 1944 and 1945, the Soviets and their Polish allies defeated and expelled the German army from Poland at a cost of over 600,000 Soviet soldiers lost.
The earliest buildings, such as Indianapolis White Castle #3, built in 1927, had exteriors of white enamel-glazed brick and interiors of enameled steel. The Indianapolis unit was in operation until 1979, making it, at the time of its closure, the longest-operating fast food restaurant in the country. The company constructed this style of building from 1924 to 1929. White Castle Building No. 8 in Minneapolis, Minnesota, originally built in 1936 and remodeled, is an example of the chain's buildings with prefabricated white porcelain enamel on steel exteriors. The building measured 28 feet (8.5 m) by 28 feet (8.5 m) and was designed to resemble the Chicago Water Tower, with octagonal buttresses, crenelated towers, and a parapet wall. The success of White Castle led to numerous imitators. Restaurants copied the distinctive architecture of White Castle buildings, as well as created confusion for consumers by using a similar name. The first of these imitators in Wichita was Little Kastle. Many competitors created their names with a play on the White Castle name. Some restaurant chains just replaced the word "Castle" with their own word (Cabin, Cap, Clock, Crescent, Diamond, Dome, Fortress, Grille, House, Hut, Kitchen, Knight, Log, Manna, Mill, Palace, Plaza, Shop, Spot, Tavern, Tower, Turret, Wonder), while others chose to replace "White" with another color or adjective (Blue, King's, Little, Magic, Modern, Prince's, Red, Royal, Silver). Some of the other imitators included Castle Blanca, Blue Beacon, Blue Bell, Blue Tower, Krystal, Red Barn, Red Lantern, and Klover Kastle.
Sources: en.wikipedia.org
Abdominal obesity is typically associated with a statistically higher risk of heart disease, hypertension, insulin resistance, and type 2 diabetes (see below). With an increase in the waist to hip ratio and overall waist circumference the risk of death increases as well. Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance, type 2 diabetes, and an increased risk of developing cardiovascular disease. It is now generally believed that intra-abdominal fat is the depot that conveys the biggest health risk. Recent validation has concluded that total and regional body volume estimates correlate positively and significantly with biomarkers of cardiovascular risk and that BVI calculations correlate significantly with all biomarkers of cardiovascular risk. Abdominal obesity is linked with higher cardiovascular events among South Asian ethnic populations.
Since TPD observes the mass of desorbed molecules, it shows what molecules are adsorbed on the surface. Moreover, TPD recognizes the different adsorption conditions of the same molecule from the differences between the desorption temperatures of molecules desorbing different sites at the surface, e.g. terraces vs. steps. TPD also obtains the amounts of adsorbed molecules on the surface from the intensity of the peaks of the TPD spectrum, and the total amount of adsorbed species is shown by the integral of the spectrum. To measure TPD, one needs a mass spectrometer, such as a quadrupole mass spectrometer or a time-of-flight (TOF) mass spectrometer, under ultrahigh vacuum (UHV) conditions. The amount of adsorbed molecules is measured by increasing the temperature at a heating rate of typically 2 K/s to 10 K/s. Several masses may be simultaneously measured by the mass spectrometer, and the intensity of each mass as a function of temperature is obtained as a TDS spectrum. The heating procedure is often controlled by the PID control algorithm, with the controller being either a computer or specialised equipment such as a Eurotherm. Other methods of measuring desorption are Thermal Gravimetric Analysis (TGA) or using infrared detectors, thermal conductivity detectors etc.
The post-bioprinting process is necessary to create a stable structure from the biological material. If this process is not well-maintained, the mechanical integrity and function of the 3D printed object is at risk. To maintain the object, both mechanical and chemical stimulations are needed. These stimulations send signals to the cells to control the remodeling and growth of tissues. In addition, in recent development, bioreactor technologies have allowed the rapid maturation of tissues, vascularization of tissues and the ability to survive transplants. Bioreactors work in either providing convective nutrient transport, creating microgravity environments, changing the pressure causing solution to flow through the cells, or adding compression for dynamic or static loading. Each type of bioreactor is ideal for different types of tissue, for example compression bioreactors are ideal for cartilage tissue.
After college, Guillaume joined the Karamu Players in Cleveland and performed in musical comedies and opera. He toured the world in 1959 as a cast member of the Broadway musical Free and Easy. He made his Broadway debut in Kwamina in 1961. His other stage appearances included Golden Boy (with Sammy Davis Jr.), Tambourines to Glory, Guys and Dolls, for which he received a Tony Award nomination, Jacques Brel is Alive and Well and Living in Paris, and Purlie. His additional roles included Katherine Dunham's Bambouche and in Fly The Blackbird. In 1964, Guillaume portrayed Sportin' Life in a revival of Porgy and Bess at New York City Center. Guillaume was a member of the Robert De Cormier Singers, performing in concerts and on television. He recorded an LP album, Columbia CS9033, titled Just Arrived, as a member of The Pilgrims, a folk trio, with Angeline Butler and Millard Williams. Columbia records producer Tom Wilson had set out to create the Pilgrims as an answer to the popular folk trio Peter, Paul and Mary. By early 1964, the Pilgrims had recorded a handful of songs and Wilson was looking for the right song for the group's debut single when a then-unknown singer/songwriter named Paul Simon arrived for a meeting with Wilson and eventually pitched his new composition, "The Sound of Silence". Wilson liked the song and had Simon record a demo for the group, but when Simon and his friend, Art Garfunkel, sang the song for Wilson in person, he signed them to a record contract instead of using it for The Pilgrims.
=== Intestinal biopsy === An intestinal biopsy must confirm lactase deficiency following discovery of elevated hydrogen in the hydrogen breath test. Modern techniques have enabled a bedside test, identifying presence of lactase enzyme on upper gastrointestinal endoscopy instruments. However, for research applications such as mRNA measurements, a specialist laboratory is required.
Sources: en.wikipedia.org
They gained promotion to the Championship following a 3–1 win over Millwall in the play-off final later that season. In September 2016, Barnsley were caught up in an ongoing scandal in English football, with assistant manager Tommy Wright alleged to have accepted "bungs" in exchange for working as an ambassador for a third-party player ownership consortium. Wright was suspended and subsequently dismissed by the club.
More recent evidence suggests that estrogen promotes cholestasis via its metabolite estradiol-17-β-D-glucuronide (E2). E2 secreted into the canaliculi by MRP2 was found to repress the transcription of bile salt export pump (BSEP), the apical ABC transporter responsible for exporting monoanionic conjugated bile acids from hepatocytes into bile canaliculi. E2 was also found to upregulate miR-148a, which represses expression of the pregnane X receptor (PXR). PXR is a nuclear receptor in hepatocytes that senses intracellular bile acid concentrations and regulates gene expression accordingly to increase bile efflux. Genetic predisposition for ICP is suggested by familial and regional clustering of cases. Several studies have implicated heterozygous mutations of the genes ABCB11 and ABCB4 in ICP, which respectively encode the canalicular transport proteins BSEP and multidrug resistance protein 3 (MDR3). MDR3 is responsible for exporting phosphatidylcholine, the major lipid component of bile, into bile canaliculi where it forms micelles with bile salts to prevent the latter from damaging luminal epithelium. Bile flow requires canalicular secretion of both bile salts and phosphatidylcholine. MDR3 mutations are an established predisposing factor, found in 16% of ICP cases. More recently, studies have demonstrated involvement of BSEP mutations in at least 5% of cases. The V444A polymorphism of ABCB11 in particular may lead to ICP by causing a reduction in hepatic BSEP expression and consequently decreased bile salt export.
A nanodisc is a synthetic model membrane system which assists in the study of membrane proteins. Nanodiscs are discoidal proteins in which a lipid bilayer is surrounded by molecules that are amphipathic molecules including proteins, peptides, and synthetic polymers. It is composed of a lipid bilayer of phospholipids with the hydrophobic edge screened by two amphipathic proteins. These proteins are called membrane scaffolding proteins (MSP) and align in double belt formation. Nanodiscs are structurally very similar to discoidal high-density lipoproteins (HDL) and the MSPs are modified versions of apolipoprotein A1 (apoA1), the main constituent in HDL. Nanodiscs are useful in the study of membrane proteins because they can solubilise and stabilise membrane proteins and represent a more native environment than liposomes, detergent micelles, bicelles and amphipols. The art of making nanodiscs has progressed past using only the MSPs and lipids to make particles, leading to alternative strategies like peptide nanodiscs that use simpler proteins and synthetic nanodiscs that do not need any proteins for stabilization.
Medical reports describing individuals affected by FOP date back to Dr. Guy Patin in 1648. FOP was originally called myositis ossificans progressiva and was thought to be caused by muscular inflammation (myositis) that caused bone formation. In 1736, London surgeon, John Freke wrote the first case report of FOP, describing a 14-year-old boy that exhibited "'many large swellings on his back, that arise from all the vertebrae of the neck and reach down to the os sacrum. They likewise arise from every rib of his body, and joining together in all parts of his back, as the ramifications of coral do, they make, as it were, a fixed bony pair of bodice." The disease was renamed by Victor A. McKusick in 1970 following the discovery that soft tissue other than muscles (e.g. ligaments) were also affected by the disease process. The best known FOP case is that of Harry Eastlack (1933–1973). His condition began to develop at the age of ten, and by the time of his death from pneumonia in November 1973, six days before his 40th birthday, his body had completely ossified, leaving him able to move only his lips. Eastlack never met another person with FOP during his lifetime. Eastlack donated his body to science and his skeleton is now at the Mütter Museum in Philadelphia, and has proven to be an invaluable source of information in the study of FOP. Another person with FOP, Carol Orzel (April 20, 1959 – February 2018), also donated her body to the museum. Her skeleton was placed on exhibit there, adjacent to Eastlack's, in February 2019.
Atoms sticking together in molecules or crystals are said to be bonded with one another. A chemical bond may be visualized as the multipole balance between the positive charges in the nuclei and the negative charges oscillating about them. More than simple attraction and repulsion, the energies and distributions characterize the availability of an electron to bond to another atom. The chemical bond can be a covalent bond, an ionic bond, a hydrogen bond or just because of Van der Waals force. Each of these kinds of bonds is ascribed to some potential. These potentials create the interactions which hold atoms together in molecules or crystals. In many simple compounds, valence bond theory, the Valence Shell Electron Pair Repulsion model (VSEPR), and the concept of oxidation number can be used to explain molecular structure and composition. An ionic bond is formed when a metal loses one or more of its electrons, becoming a positively charged cation, and the electrons are then gained by the non-metal atom, becoming a negatively charged anion. The two oppositely charged ions attract one another, and the ionic bond is the electrostatic force of attraction between them. For example, sodium (Na), a metal, loses one electron to become an Na+ cation while chlorine (Cl), a non-metal, gains this electron to become Cl−. The ions are held together due to electrostatic attraction, and that compound sodium chloride (NaCl), or common table salt, is formed.
Sources: en.wikipedia.org
It is a synthetic cyclic peptide that acts as an agonist at melanocortin receptors. It is not a hormone replacement therapy and not a vasodilator in the usual clinical sense, although it does affect vascular tone. Chemically it belongs to the melanocortin analogue family.
PT-141 was the internal development code used during early research and it persists in older publications, conference abstracts, and informal listings. The code and the approved name refer to the same molecule. Its continued use reflects habit in the literature rather than any difference in substance.
No. The intranasal form was studied in trials but was never approved, and absorption through the nasal route varies considerably between individuals. Approved labelling covers a subcutaneous injection only. Any nasal product sold outside regulated channels falls outside verified manufacturing.
The peptide is polar and charged, and reversed-phase chromatography with acidic mobile phases resolves it well from related substances. Ultraviolet detection near 214 nm gives adequate sensitivity without derivatisation.