| Identification | Back Directory | [Name]
PT-141 | [CAS]
189691-06-3 | [Synonyms]
Brmelanotice
REMELANOTIDE
BREMELANOTIDE
PT-141 USP/EP/BP
BREMELANOTIDE PT141
Bremelanotide
See B677355
Bremelanotide, PT141,PT-141
Bremelanotide,α-MSH (PT-141)
PT-141(Bremelanotide) acetate
PT141 Acetate,BreMelanotide Acetate
Bremelanotide powder, PT-141 Acetate
Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)
Ac-Nle-cyclo(-Asp-His-D-Phe-Arg-Trp-Lys)-OH
L-Lysine, N-acetyl-L-norleucyl-L-α-aspartyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-, (2→7)-lactam
N-Acetyl-L-norleucyl-L-alpha-aspartyl-L-histidyl-D-phenylalanyl-L-arginyl-L-tryptophyl-L-lysine (2-7)-lactam | [EINECS(EC#)]
211-519-9 | [Molecular Formula]
C50H68N14O10 | [MDL Number]
MFCD09954110 | [MOL File]
189691-06-3.mol | [Molecular Weight]
1025.18 |
| Chemical Properties | Back Directory | [density ]
1.43 | [solubility ]
DMSO (Slightly), Methanol (Slightly), Water (Slightly, Sonicated) | [form ]
Solid | [pka]
3.37±0.70(Predicted) | [color ]
White to Off-White | [Sequence]
Ac-Nle-Asp-His-D-Phe-Arg-Trp-Lys-OH Asp-Lys | [Stability:]
Un-reconstituted lyophilized powder should be stored under refrigeration per vial’s instruction. After reconstitution with bacteriostatic water, refrigerate solution and use within 30 days. If buffered solution is used, stability will improve. | [InChIKey]
FFHBJDQSGDNCIV-MLYCVURTNA-N |
| Hazard Information | Back Directory | [Description]
Bremelanotide (Vyleesi®) was approved by the FDA in June 2019 for the treatment of acquired, generalized HSDD in premenopausal women. Bremelanotide activates melanocortin receptors，but the mechanism by which it improves sexual desire is unknown. To use bremelanotide, women inject it under the skin ofthe abdomen or thigh at least 45 minutes before anticipated sexual activity.The optimal time to inject bremelanotide may vary based on the duration of benefit and side effects experienced. More than one dose of bremelanotide should not be used within 24 hours or more than eight doses per month. Common side effects include nausea, vomiting, flushing, injection site reactions, and headache. Bremelanotide should not be used in women with high blood pressure that is uncontrolled or in those with known cardiovascular disease, and it is not recommended for women at high risk for cardiovascular disease. The safety and efficacy of bremelanotide has not been studied in breast cancer survivors, and there are no recommendations regarding its use in this population. | [Uses]
Treatment of
sexual dysfunction (melanocortin receptor agonist). | [Definition]
ChEBI: Bremelanotide is an oligopeptide. | [Biological Activity]
Bremelanotide (PT-141) is a brain-penetrant, alpha-melanocyte-stimulating hormone (α-MSH)-derived cyclic heptapeptide agonist toward melanocortin receptors, including MC1R, MC3R and MC4R (affinty = 10 nM by competitive binding against 0.2 nM NDP-α-MSH using human MC4R-expressing HEK-293). Bremelanotide induces cAMP accumulation in hMC4R-expressing HEK-293 cells and exhibits in vivo sexual arousal efficacy among both male (50 μg/kg intranasally or 50-500 pg/kg via lateral ventricle injection) and female rats (100-200 μg/kg sc or 800 μg/kg via lateral ventricle injection) by activating neurons in brain regions responsible for sexual function. | [Mechanism of action]
The trade name is vylessi. It likely works in the brain, but the true mechanism of action is unknown.Bremelanotide is given by injection at least forty-five minutes prior to anticipated sex and alcohol must be avoided for two hours before and two hours after using the medication.
Bremelanotide is a nonselective melanocortin receptor agonist; at therapeutic doses, bremelanotide binding to melanocortin 1 and 4 receptors is mostrelevant.
Sexual dysfunction is theoretically linked to an imbalance in central excitatory and inhibitory sexual signals.
HSDD hypothetically results from excessive inhibitory signals, inadequate excitatory signals, or a combination of the two.
Melanocortin receptors are located in the medial preoptic area of the hypothalamus, which is implicated in the sexual behavior of both sexes; stimulation of those receptors leads to dopamine release.
Prescriber's Guide Stahl's Essential Psychopharmacology | [Clinical Use]
bremelanotide, or PT-141, is a synthetic, central melanocortin receptor agonist that increases αmelanocyte stimulating hormone (α-MSH) in the body. It has been reported to aid in sexual experiences for men and women.PT-141 is a deaminated derivative and likely metabolite of Melanotan II, another synthetic melanocortin receptor agonist initially used for tanning purposes. During treatment with Melanotan II, researchers, clinicians and patients noticed an increase in sexual activity.However, Side effects reported with melanotan II include nausea, vomiting, yawning, and a delayed onset of erection (approximately 2 hours).So researchers began to look for alternatives to melanotan II, and bremelanotide was synthesized in 2000 and trials began.
Unlike the FDA approved PDE5 inhibitors that improved sexual function by improving nitric oxide and vascular function, PT-141 works on the CNS, thus eliciting a more desirous sexual response.Of the 5 meanocortin receptors (1-5), PT-141 has the highest affinity for melanocortin receptor 4 (MC4R). In the hypothalamus, α-MSH suppresses appetite (MC4R receptor), with MC4R defects are reported to be a cause for autosomal dominant obesity, accounting for approximately 6% of all cases of early onset obesity.MC4R stimulation also contributes to improved sexual function in both men (improving penile erections) and women (increasing desire and arousal).
https://northamptonintegrativemedicine.com | [Side effects]
The U.S. Food and Drug Administration today approved Vyleesi (bremelanotide) to treat acquired, generalized hypoactive sexual desire disorder (HSDD) in premenopausal women.
The most common side effects of Vyleesi are nausea and vomiting, flushing, injection site reactions and headache. About 40% of patients in the clinical trials experienced nausea, most commonly with the first Vyleesi injection, and 13% needed medications for the treatment of nausea. About 1% of patients treated with Vyleesi in the clinical trials reported darkening of the gums and parts of the skin, including the face and breasts, which did not go away in about half the patients after stopping treatment. Patients with dark skin were more likely to develop this side effect.
https://www.fda.gov | [Synthesis]
A kind of synthetic method of Bremelanotide, by the carboxyl of Lys with
protecting to hydroxymethyl-benzoic acid.Can be the connection
P-hydroxybenzoic acid gene on vector resin, then with Fmoc-Lys
(IVDde）There is esterification in-OH, aminoacid is sequentially
ingressed into again, obtain Boc-His (Trt)-D-Phe-Arg (pbf)-TrP (Boc)-Lys
(IVDde)-HMBA-P, then protection group IVDde on Lys is taken off with
lysate, the amino group for exposing, be there is into condensation
reaction in the carboxyl of Asp in the amino group for exposing and
Ac-Nle-Asp (COOH)-otBu and obtain condensation liquid, condensation
liquid is cracked, filter to take filtrate, sedimentation, centrifuging
and taking lower floor solid, it is vacuum dried to obtain thick
peptide, thick peptide is cyclized must be cyclized liquid, cyclisation
liquid is hydrolyzed, again after preparative high performance liquid
chromatography is isolated and purified, lyophilization obtains
Bremelanotide sterling. Sterling is detected, purity is more than 98%,
response rate 50%-60%. | [Current market and forecast]
Uptake of Vyleesi (bremelanotide), a drug produced by Amag Pharmaceuticals to treat women with HSDD, is expected to be slow, if approved, but is unlikely to encounter the same challenges as Sprout's Addyi, an already approved similar drug.
Bremelanotide (marketed as Vyleesi) — an injectable drug approved in June for premenopausal women with generalized hypoactive sexual desire disorder — will carry a list price of $899, Reuters reports. | [References]
[1] Synthesis method of Bremelanotide. CN106589111A |
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