Absorption, Distribution and Excretion
Bremelanotide has a Tmax or 1.0 hour (0.5-1.0 hours) and is 100% bioavailable. The Cmax is 72.8ng/mL and the AUC is 276hr\*ng/mL.
64.8% of a radiolabelled dose is excreted in the urine and 22.8% of the dose is recovered in the feces.
The mean volume of distribution of bremelanotide is 25.0±5.8L.
The mean clearance of bremelanotide is 6.5±1.0L/hr.

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Metabolism / Metabolites
Bremelanotide is a 7 amino acid and so its metabolism consists of multiple hydrolysis reactions.

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Biological Half-Life
The half life of bremelanotide is 2.7 hours (1.9-4.0 hours).

Hepatotoxicity
In preregistration clinical trials, serum enzyme elevations were reported in small numbers of bremelanotide treated patients but in a similar proportion of subjects receiving placebo. A single case of acute hepatitis arose in a patient who had received 10 injections of bremelanotide over a one year period with marked elevations in serum aminotransferase levels, minimal increases in alkaline phosphatase, and mild jaundice which resolved after discontinuation. There have been no instances of acute liver failure or chronic liver injury attributed to bremelanotide, but the total clinical experience with this drug has been limited. Thus, acute liver injury from bremelanotide may occur but is rare.
Likelihood score: D (possible rare cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
No information is available on the clinical use of bremelanotide during breastfeeding. Because bremelanotide is a cyclic peptide molecule with a molecular weight of 1025, the amount in milk is likely to be very low and absorption is unlikely because it is probably destroyed in the infant's gastrointestinal tract. Until more data become available, bremelanotide should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

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Protein Binding
Bremelanotide is 21% protein bound in serum.

[1]. Bremelanotide: an overview of preclinical CNS effects on female sexual function. J Sex Med. 2007 Nov;4 Suppl 4:269-79.

[2]. PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003 Jun;994:96-102.

Bremelanotide is an oligopeptide.
Bremelanotide is a 7 amino acid peptide used to treat hypoactive sexual desire disorder in premenopausal women. Bremelanotide does not interact with alcohol. The mechanism by which bremelanotide's action on receptors translates to a clinical effect is still unknown. Bremelanotide was first described in the literature in 2003 when it was known by the investigational code PT-141. Since then it was investigated for its place in treating sexual dysfunction in men and women but is now only indicated for women. Other drugs used to treat female sexual dysfunction include [flibanserin], [estrogen], [ospemifene], and [prasterone]. Bremelanotide was granted FDA approval on 21 June 2019.
Bremelanotide is a Melanocortin Receptor Agonist. The mechanism of action of bremelanotide is as a Melanocortin Receptor Agonist.
Bremelanotide is a parenterally administered melanocortin receptor agonist that is used to treat female hypoactive sexual desire disorder. Bremelanotide has been reported to cause mild serum enzyme elevations during therapy and has been implicated in rare instances of clinically apparent acute liver injury.
See also: Bremelanotide Acetate (active moiety of).

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Drug Indication
Bremelanotide is indicated to treat premenopausal women with hypoactive sexual desire disorder that is not due to a medical or psychiatric condition, problems with the relationship, or the effects of a medication or drug.

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Mechanism of Action
Bremelanotide is an agonist of many melanocortin receptors which in order of potency are MC1R, MC4R, MC3R, MC5R, and MC2R. The mechanism by which agonism of these receptors translates to an improvement in hypoactive sexual desire disorder is currently unknown, however MC4R receptors are present in many areas of the central nervous system. MC3R and MC4R are found in the hypothalamus and are involved in food intake and energy homeostasis. One theory is that bremelanotide stimulates dopamine in the medial preoptic area, which is involved in the sexual behaviour of a number of organisms.

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Pharmacodynamics
Bremelanotide is a melanocortin receptor agonist injected 45 minutes before anticipated sexual activity. Agonism of the melanocortin receptor MC1R also leads to increased melanin expression. Patients taking bremelanotide may also experience nausea, headache, and vomiting.

C50H68N14O10

1025.18

1024.524

C, 58.58; H, 6.69; N, 19.13; O, 15.61

189691-06-3

Bremelanotide Acetate; 1607799-13-2

9941379

Nle-D(1)HFRWK(1)

Solid powder

1.4±0.1 g/cm3

1.679

-1.21

13

12

17

74

1950

7

CCCC[C@H](NC(C)=O)C(N[C@H]1CC(NCCCC[C@H](NC([C@@H](NC([C@@H](NC([C@H](NC([C@@H](NC1=O)CC2=CN=CN2)=O)CC3=CC=CC=C3)=O)CCCNC(N)=N)=O)CC4=CNC5=CC=CC=C45)=O)C(O)=O)=O)=O

FFHBJDQSGDNCIV-MFVUMRCOSA-N

InChI=1S/C50H68N14O10/c1-3-4-16-35(58-29(2)65)43(67)64-41-25-42(66)54-20-11-10-18-37(49(73)74)60-46(70)39(23-31-26-56-34-17-9-8-15-33(31)34)62-44(68)36(19-12-21-55-50(51)52)59-45(69)38(22-30-13-6-5-7-14-30)61-47(71)40(63-48(41)72)24-32-27-53-28-57-32/h5-9,13-15,17,26-28,35-41,56H,3-4,10-12,16,18-25H2,1-2H3,(H,53,57)(H,54,66)(H,58,65)(H,59,69)(H,60,70)(H,61,71)(H,62,68)(H,63,72)(H,64,67)(H,73,74)(H4,51,52,55)/t35-,36-,37-,38+,39-,40-,41-/m0/s1

3S,6S,9R,12S,15S,23S)-15-[[(2S)-2-acetamidohexanoyl]amino]-9-benzyl-6-[3-(diaminomethylideneamino)propyl]-12-(1H-imidazol-5-ylmethyl)-3-(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexazacyclotricosane-23-carboxylic acid

PT-141; PT141; Bremelanotide; PT 141

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.

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Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution.
Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)
Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil)
Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals).

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Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)]
*Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline)

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Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium)
Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose
Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals).

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Oral Formulation 3: Dissolved in PEG400
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

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Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

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 (Please use freshly prepared in vivo formulations for optimal results.)