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PT-141 is the original development code for bremelanotide, a synthetic peptide first studied as a potential tanning and sexual-response agent in the 1990s. Researchers at a small American biotechnology firm designed it as a shortened analogue of melanotan II, which itself came from work on alpha-melanocyte-stimulating hormone. Early screening focused on pigmentation, but behavioural observations in animal models redirected attention toward sexual motivation. That shift made PT-141 one of the first melanocortin compounds investigated specifically for effects on desire rather than on skin colour.
Clinical development proceeded through two routes of administration. An intranasal formulation advanced first, but variable absorption and tolerability problems led to a switch to subcutaneous injection. The United States Food and Drug Administration approved the subcutaneous product in 2019 for hypoactive sexual desire disorder in premenopausal women. Marketing rights subsequently changed hands, and commercial availability has fluctuated since approval. Use in men, in postmenopausal women, and in combination with other agents remains outside the approved label.
Bremelanotide acts as an agonist at several melanocortin receptors, with the strongest reported activity at MC4R and measurable activity at MC1R and MC3R. Because MC4R is expressed in hypothalamic and limbic circuits, the proposed mechanism links receptor activation to modulation of central pathways involved in desire rather than to direct effects on peripheral genital tissue. The precise downstream steps remain incompletely characterized, and evidence for the involvement of specific neurotransmitters is suggestive rather than settled. Nausea and blood pressure elevation reported during trials are consistent with melanocortin signaling outside the intended target circuit.
Compared with melanotan II, bremelanotide is a smaller cyclic peptide with a more constrained backbone, which affects receptor selectivity and metabolic stability. Published descriptions give a plasma half-life on the order of a few hours after subcutaneous administration, with elimination through hepatic and renal routes and limited plasma protein binding. Central access is inferred from effects observed in animal models, although direct measurement in humans is limited. Handling and storage requirements follow from the peptide backbone, which is susceptible to hydrolysis and oxidation.
The melanocortin system comprises five G protein-coupled receptors, designated MC1 through MC5, that signal mainly through cyclic AMP accumulation. MC1R and MC2R are associated with pigmentation and adrenal steroid production, while MC3R and MC4R are expressed in the central nervous system and influence energy balance and behavior. MC5R appears in exocrine tissues. Natural agonists include alpha-melanocyte-stimulating hormone and adrenocorticotropic hormone, and endogenous antagonists such as agouti-related protein modulate the same sites. This receptor family provides the framework within which bremelanotide activity is described.
| Property | Value | Notes |
|---|---|---|
| Molecular formula | C50H68N14O10 | Free base; the drug product is formulated as an acetate salt |
| Molar mass | About 1025 g/mol | Calculated for the free base |
| Appearance | White to off-white lyophilized powder | Typical form of research-grade material |
| CAS Registry Number | 189691-06-3 | Common listing for the free base |
| Typical storage | -20 °C, desiccated, protected from light | Repeated freeze-thaw cycles are best avoided |
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.
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.
After subcutaneous dosing, peak plasma concentrations appear within roughly one hour, and elimination is fast, with a half-life on the order of a few hours. Degradation is mainly proteolytic, and at least one circulating fragment retains receptor activity, so parent-drug levels alone do not describe total exposure. Clearance does not depend heavily on hepatic cytochrome enzymes, which lowers the likelihood of common metabolic interaction routes. Data in renal or hepatic impairment are limited. Repeated dosing does not appear to produce marked accumulation given the short half-life.
Reported pharmacodynamic effects include transient rises in blood pressure and heart rate, flushing, nausea and headache, appearing soon after dosing and resolving within hours. These responses were dose-related in early studies and shaped the label's cardiovascular cautions and blood pressure monitoring advice. Gastrointestinal upset is the most frequent reason cited for discontinuation in trials. Whether the vascular signal attenuates with repeated use is not settled. Central effects on desire are described as emerging over weeks rather than immediately, which points to a cumulative rather than acute process.
Lyophilized peptide arrives as a white to off-white cake or powder and is normally held at minus twenty degrees Celsius or colder for extended periods. Short-term bench work at ambient temperature is tolerable for minutes, not hours, because the solid is hygroscopic and picks up moisture that promotes hydrolysis. Vials should stay in a desiccator or a sealed bag with desiccant, protected from light, since aromatic residues in the sequence are susceptible to photo-oxidation. Inventory records that note arrival date and storage location reduce the chance of using degraded material.
Reconstitution is usually performed with sterile water or a dilute acetic acid solution, and the choice of solvent affects both dissolution speed and final pH. Complete dissolution should be confirmed by visual inspection before any aliquot is taken, since undissolved particles can concentrate in the sampling volume. Repeated freeze-thaw cycles are the most common cause of gradual loss of purity, so dividing a stock into single-use aliquots at the first opportunity is standard practice. Working solutions kept refrigerated are generally used within days rather than weeks.
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.
The peptide contains seven amino acids arranged in a ring, closed by a lactam bridge between a side-chain acid and an amine. This cyclic constraint holds the backbone in a defined conformation and increases resistance to enzymatic breakdown relative to linear analogs. N-terminal acetylation and a C-terminal amide further protect the molecule from exopeptidases. The result is a compound with a comparatively long circulation time for a small peptide. Structural modification of the bridge alters receptor affinity, which is one reason analogs in this family differ in their subtype preferences.
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.
== Mechanism of action == BDNF binds at least two receptors on the surface of cells that are capable of responding to this growth factor, TrkB (pronounced "Track B") and the LNGFR (for low-affinity nerve growth factor receptor, also known as p75). It may also modulate the activity of various neurotransmitter receptors, including the Alpha-7 nicotinic receptor. BDNF has also been shown to interact with the reelin signaling chain. The expression of reelin by Cajal–Retzius cells goes down during development under the influence of BDNF. The latter also decreases reelin expression in neuronal culture.
== Background == During the Trump administration's second term, the US intensified its focus on drug cartels, characterizing the smugglers as terrorists. In August 2025, the US deployed warships and personnel to the Caribbean, citing the need to combat drug cartels. PBS News reported that Trump was using the military to counter cartels he blamed for trafficking fentanyl and other illicit drugs into the US and for fueling violence in American cities.
The likelihood of ionization is a function of the filament temperature, the work function of the filament substrate and the ionization energy of the element. This is summarised in the Saha–Langmuir equation:
== Interactions == Concomitant use of tizanidine and moderate or potent CYP1A2 inhibitors (such as zileuton, certain antiarrhythmics (amiodarone, mexiletine, propafenone, verapamil), cimetidine, famotidine, aciclovir, ticlopidine and oral contraceptives) is contraindicated. Concomitant use of tizanidine with fluvoxamine, a potent CYP1A2 inhibitor in humans, resulted in a 33-fold increase in the tizanidine AUC (plasma drug concentration-time curve). For this reason fluvoxamine and tizanidine should not be taken at the same time. Fluoroquinolone antibiotics such as moxifloxacin, levofloxacin, and ciprofloxacin should also be avoided due to an increased serum concentration of tizanidine when administered concomitantly. Tizanidine has the potential to interact with other central nervous system depressants. Alcohol should be avoided, particularly as it can upset the stomach. The CNS-depressant effects of tizanidine and alcohol are additive. Caution with the following interactions:
Sources: en.wikipedia.org
There is significant controversy about the level of risk of stroke from neck manipulation. It may be that manipulation can cause dissection, or it may be that the dissection is already present in some people who seek manipulative treatment. At this time, conclusive evidence does not exist to support either a strong association between neck manipulation and stroke, or no association. However, the two most authoritative articles on the subject, recent literature reviews and analyses, conclude that although there exists an association between stroke from vertebral artery dissection and chiropractic adjustment, there is insufficient evidence to indicate that the adjustment caused the dissection. A recent meta-analysis of the published data on the topic also looked to apply Hill's criteria for assigning causation in biological systems to the relationship between chiropractic adjustment and cervical artery dissection, finding that the relationship did not fulfill the required criteria for causality.
== Places == Central provinces (disambiguation) (C.P.) Central Provinces (1861–1936), a former province of India, succeeded by Central Provinces and Berar (1936–1950), corresponding to Madhya Pradesh in the post-partition republic Central Provinces and Berar Circuit or C. P.-Berar Circuit, a Hindi film distribution circuit comprising parts of Madhya Pradesh, Chhattisgarh and Maharashtra Clipperton Island, a territory with exceptional country code CP
== Centenarians in antiquity == While the number of centenarians per capita was much lower in ancient times than today, the data suggest that they were not unheard of. Estimates of life expectancy in antiquity are far lower than modern values largely due to the far greater incidence of deaths in infancy or childhood, though adult mortality was also considerably greater than today. The assumption of what constitutes "old age", or being "elderly", at least, seems to have remained unchanged since antiquity, the line being generally drawn at either sixty or sixty-five years; Psalm 90:10 in the Hebrew Bible appears to give seventy to eighty years as the natural life expectancy of a person surviving into old age, "The years of our life are seventy, or even by reason of strength eighty". A survey of the lifespans of male individuals with entries in the Oxford Classical Dictionary (i.e., a sample pre-selected to include those who lived long enough to attain historical notability) found a median lifespan of 72 years, and a range of 32 to 107 years, for 128 individuals born before 100 BC (though the same study found a median lifespan of 66 years for 100 individuals born after 100 BC but no later than 602 AD); by comparison, male individuals listed in Chambers Biographical Dictionary who died between 1900 and 1949 had a median lifespan of 71.5 years, with a range between 29 and 105 years. But as indicated above, far fewer in antiquity survived even from early adulthood to such advanced age – probably under a fifth, compared to a global average of two-thirds today.
== History == In the 18th century, William Withering discovered that arsenic trioxide, when used in small doses, exhibited therapeutic effects. During the same period, Thomas Fowler prepared a 1% solution of arsenic and potassium carbonate, which was used to treat skin diseases (primarily psoriasis) until the 20th century. An arsenic-based drug, arsphenamine, was also developed for the treatment of syphilis, synthesized by Paul Ehrlich, though it was eventually replaced by penicillin. Arsenic compounds were widely used to treat various diseases in the 19th and early 20th centuries. The first reports of the anticancer activity of arsenic trioxide date back to 1878, when a report from Boston City Hospital described Fowler's solution lowering leukocyte levels in the blood of two healthy individuals and one patient. Arsenic trioxide continued to be used in the treatment of leukemia until the introduction of radiotherapy. It made a resurgence in the 1930s when the first studies confirmed the high efficacy of arsenic trioxide in treating chronic myelogenous leukemia. In the late 1960s, physicians working at the Harbin Medical Academy in China were sent to a center focusing on traditional Chinese medicine, where they used a melanoma ointment, with arsenic as its main ingredient. At that time, the arsenal of anticancer drugs was limited, prompting doctors to experiment with arsenic. Early trials used oral administration, but it showed strong toxic effects. In March 1971, the first trials of intravenous arsenic began, which showed significantly lower toxicity.
==== Style periods ==== A broad classification of styles, formalized by Le Coq and Waldschmidt in 1933, has been generally accepted. The first style is called "Indo-Iranian style I", and cover all the early caves with delicate tone-on-tone paintings, using browns, oranges and greens. The name "Indo-Iranian" broadly denotes the artistic influence from India, combined with elements of Iranian art, that presided over the creation of the first cave paintings at Kizil. The main representative caves of this style are the Cave of the Hippocampi (Cave 118), the Cave of the Painters (Cave 207), the Peacock Cave (Cave 76), the Overpainted Cave (Cave 117), the Cave of the Statues (Cave 77), and the Cave of the Seafarers (Cave 112). The small group of the Treasure Cave (Cave 83, 84) is considered as contemporary, but in a slightly personal style, sometimes called "Special Style" (Sonderstil). The first style is only found in Kizil, except for one cave in nearby Kumtura: the Cave with the cupola. The second style is called "Indo-Iranian style II", and cover most of the other caves of Kizil, which use strongly contrasted colors and strong line strokes, using browns, oranges and greens and especially a vivid lapis-lazuli blue. The name "Indo-Iranian" again broadly denotes the artistic influence from India, combined with important influences from Central Asian and the Iranian world. This style is further divided in three broad periods. Finally, a third Uighur-Chinese style appears in only two caves at Kizil.
Sources: en.wikipedia.org
PT-141 is a research code for bremelanotide, a cyclic peptide that activates melanocortin receptors. It was developed for sexual dysfunction and later approved under a brand name as a subcutaneous injection. The same code is widely used by suppliers selling non-pharmaceutical material.
Both are synthetic melanocortin agonists and share a similar peptide backbone, but they are distinct molecules with different receptor profiles. Melanotan II was never approved as a medicine, whereas bremelanotide was. Findings about one compound should not be transferred to the other without direct evidence.
It is typically distributed as a lyophilized powder in sealed vials, sometimes with a separate solvent. Purity statements usually originate from the supplier rather than an independent laboratory. Storage recommendations vary between vendors, which makes comparison across sources difficult.
Reported activity is highest at MC4R, with lower potency at MC1R and MC3R. The MC4R interaction is generally treated as the most relevant to its central effects. Selectivity is not absolute, and activity across the family is dose-dependent.