Bremelanotide

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

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Name
Bremelanotide
Accession Number
DB11653
Type
Small Molecule
Groups
Approved, Investigational
Description

Bremelanotide is a 7 amino acid peptide used to treat hypoactive sexual desire disorder in premenopausal women.5 Bremelanotide does not interact with alcohol.2 The mechanism by which bremelanotide's action on receptors translates to a clinical effect is still unknown.5

Bremelanotide was first described in the literature in 2003 when it was known by the investigational code PT-141.1 Since then it was investigated for its place in treating sexual dysfunction in men and women but is now only indicated for women.1,2,5 Other drugs used to treat female sexual dysfunction include flibanserin, estrogen, ospemifene, and prasterone.3

Bremelanotide was granted FDA approval on 21 June 2019.5

Structure
Thumb
Synonyms
  • Bremelanotide
External IDs
PT 141 / PT-141
Categories
UNII
6Y24O4F92S
CAS number
189691-06-3
Weight
Average: 1025.182
Monoisotopic: 1024.524284446
Chemical Formula
C50H68N14O10
InChI Key
FFHBJDQSGDNCIV-MFVUMRCOSA-N
InChI
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
IUPAC Name
(3S,6S,9R,12S,15S,23S)-9-benzyl-6-(3-carbamimidamidopropyl)-15-[(2S)-2-acetamidohexanamido]-12-[(1H-imidazol-5-yl)methyl]-3-[(1H-indol-3-yl)methyl]-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,18-hexaazacyclotricosane-23-carboxylic acid
SMILES
CCCC[C@H](NC(C)=O)C(=O)N[C@H]1CC(=O)NCCCC[C@H](NC(=O)[C@H](CC2=CNC3=CC=CC=C23)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](CC2=CC=CC=C2)NC(=O)[C@H](CC2=CN=CN2)NC1=O)C(O)=O

Pharmacology

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.5

Associated Conditions
Pharmacodynamics

Bremelanotide is a melanocortin receptor agonist injected 45 minutes before anticipated sexual activity.5 Agonism of the melanocortin receptor MC1R also leads to increased melanin expression.5 Patients taking bremelanotide may also experience nausea, headache, and vomiting.5

Mechanism of action

Bremelanotide is an agonist of many melanocortin receptors which in order of potency are MC1R, MC4R, MC3R, MC5R, and MC2R.5 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.5 MC3R and MC4R are found in the hypothalamus and are involved in food intake and energy homeostasis.1

One theory is that bremelanotide stimulates dopamine in the medial preoptic area, which is involved in the sexual behaviour of a number of organisms.4

TargetActionsOrganism
UMelanocyte-stimulating hormone receptor
agonist
Humans
UMelanocortin receptor 4
agonist
Humans
UMelanocortin receptor 3
agonist
Humans
UMelanocortin receptor 5
agonist
Humans
UAdrenocorticotropic hormone receptor
agonist
Humans
Absorption

Bremelanotide has a Tmax or 1.0 hour (0.5-1.0 hours) and is 100% bioavailable.5 The Cmax is 72.8ng/mL and the AUC is 276hr*ng/mL.5

Volume of distribution

The mean volume of distribution of bremelanotide is 25.0±5.8L.5

Protein binding

Bremelanotide is 21% protein bound in serum.5

Metabolism

Bremelanotide is a 7 amino acid and so its metabolism consists of multiple hydrolysis reactions.5

Route of elimination

64.8% of a radiolabelled dose is excreted in the urine and 22.8% of the dose is recovered in the feces.5

Half life

The half life of bremelanotide is 2.7 hours (1.9-4.0 hours).5

Clearance

The mean clearance of bremelanotide is 6.5±1.0L/hr.5

Toxicity

Currently there are no reports of overdoses of bremelanotide.5 Patients taking higher doses are more likely to experience nausea, focal hyperpigmentation, and increases in blood pressure.5 In the event of an overdose, supportive measures should be used to address the associated symptoms.5

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
NaltrexoneThe serum concentration of Naltrexone can be decreased when it is combined with Bremelanotide.
Additional Data Available
  • Extended Description
    Extended Description

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  • Severity
    Severity

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  • Evidence Level
    Evidence Level

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  • Action
    Action

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Food Interactions
Not Available

References

General References
  1. Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY: PT-141: a melanocortin agonist for the treatment of sexual dysfunction. Ann N Y Acad Sci. 2003 Jun;994:96-102. doi: 10.1111/j.1749-6632.2003.tb03167.x. [PubMed:12851303]
  2. Clayton AH, Lucas J, DeRogatis LR, Jordan R: Phase I Randomized Placebo-controlled, Double-blind Study of the Safety and Tolerability of Bremelanotide Coadministered With Ethanol in Healthy Male and Female Participants. Clin Ther. 2017 Mar;39(3):514-526.e14. doi: 10.1016/j.clinthera.2017.01.018. Epub 2017 Feb 9. [PubMed:28189361]
  3. Miller MK, Smith JR, Norman JJ, Clayton AH: Expert opinion on existing and developing drugs to treat female sexual dysfunction. Expert Opin Emerg Drugs. 2018 Sep;23(3):223-230. doi: 10.1080/14728214.2018.1527901. Epub 2018 Oct 11. [PubMed:30251897]
  4. Both S: Recent Developments in Psychopharmaceutical Approaches to Treating Female Sexual Interest and Arousal Disorder. Curr Sex Health Rep. 2017;9(4):192-199. doi: 10.1007/s11930-017-0124-3. Epub 2017 Oct 19. [PubMed:29225554]
  5. FDA approvals [Link]
External Links
PubChem Compound
9941379
PubChem Substance
347828024
ChemSpider
8116997
BindingDB
50389769
ChEMBL
CHEMBL2070241
Wikipedia
Bremelanotide
MSDS
Download (526 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1RecruitingTreatmentNausea1
2CompletedNot AvailableSexual arousal disorders1
2CompletedTreatmentFemale Sexual Arousal Disorder / Hypoactive Sexual Desire Disorder (HSDD)1
3CompletedTreatmentHypoactive Sexual Desire Disorder (HSDD)2

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
boiling point (°C)230MSDS
Predicted Properties
PropertyValueSource
Water Solubility0.0251 mg/mLALOGPS
logP0.69ALOGPS
logP-3.2ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)3.45ChemAxon
pKa (Strongest Basic)11.96ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count14ChemAxon
Hydrogen Donor Count14ChemAxon
Polar Surface Area376.47 Å2ChemAxon
Rotatable Bond Count17ChemAxon
Refractivity278.91 m3·mol-1ChemAxon
Polarizability107.49 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability0ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as oligopeptides. These are organic compounds containing a sequence of between three and ten alpha-amino acids joined by peptide bonds.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Oligopeptides
Alternative Parents
Cyclic peptides / N-acyl-alpha amino acids and derivatives / Macrolactams / Alpha amino acid amides / 3-alkylindoles / Imidazolyl carboxylic acids and derivatives / Benzene and substituted derivatives / Substituted pyrroles / N-acyl amines / Acetamides
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Substituents
Alpha-oligopeptide / Cyclic alpha peptide / Macrolactam / N-acyl-alpha amino acid or derivatives / Alpha-amino acid amide / N-substituted-alpha-amino acid / Alpha-amino acid or derivatives / 3-alkylindole / Indole / Indole or derivatives
show 31 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Ubiquitin protein ligase binding
Specific Function
Receptor for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase.
Gene Name
MC1R
Uniprot ID
Q01726
Uniprot Name
Melanocyte-stimulating hormone receptor
Molecular Weight
34705.04 Da
2. Melanocortin receptor 4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
3. Melanocortin receptor 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
4. Melanocortin receptor 5
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Agonist
General Function
Melanocortin receptor activity
Specific Function
Receptor for corticotropin (ACTH). This receptor is mediated by G proteins (G(s)) which activate adenylate cyclase (cAMP).
Gene Name
MC2R
Uniprot ID
Q01718
Uniprot Name
Adrenocorticotropic hormone receptor
Molecular Weight
33926.28 Da

Drug created on October 20, 2016 14:37 / Updated on June 26, 2019 06:06