Bremelanotide

From Self-sufficiency
Jump to: navigation, search
Bremelanotide
350px
Systematic (IUPAC) name
(3R,6R,9S,12R,15R,23R)-15-{[(2R)-2-

Acetamidohexanoyl]amino}-9-benzyl- 6-(3-carbamimidamidopropyl)-12- (1H-imidazol-5-ylmethyl)-3-(1H-indol- 3-ylmethyl)-2,5,8,11,14,17-hexaoxo- 1,4,7,10,13,18-hexaazacyclotricosane

-23-carboxylic acid
Legal status
Legal status
  • US: Unscheduled
Identifiers
CAS Number 189691-06-3
ATC code none
PubChem CID 9941379
ChemSpider 8116997
Chemical data
Formula C50H68N14O10
Molar mass 1025.2[[Script error: No such module "String".]]
Script error: No such module "collapsible list".
  (verify)
Script error: No such module "TemplatePar".Expression error: Unexpected < operator.

Bremelanotide (pronounced /ˌbrɛmɨˈlænətaɪd/ (13px listen)) (formerly PT-141) is a compound under drug development by Palatin Technologies as a treatment for hemorrhagic shock and reperfusion injury. It functions by activating the melanocortin receptors MC1R and MC4R, to modulate inflammation and limiting ischemia.[1] It was originally developed for use in treating sexual dysfunction but this application was temporarily discontinued in 2008, after concerns were raised over adverse side effects of increased blood pressure. Currently, Palatin is in negotiations with the FDA to resume Human Phase 2 studies using a new subcutaneous drug delivery system that appears to have little effect on blood pressure.

Development

Bremelanotide was developed from the peptide Melanotan II which underwent testing as a sunless tanning agent. In initial testing, Melanotan II did induce tanning but additionally caused sexual arousal and spontaneous erections as unexpected side effects in nine out of the ten original male volunteer test subjects.[2]

In studies, bremelanotide was shown to induce lordosis in an animal model[3] and was also effective in treating sexual dysfunction in both men (erectile dysfunction or impotence) and women (sexual arousal disorder). Unlike Viagra and other related medications, it does not act upon the vascular system, but directly increases sexual desire via the nervous system.[4]

A Phase III clinical trial was scheduled to begin in the first half of 2007, but was delayed until August 2007. On August 30, Palatin announced that the U.S. Food and Drug Administration had expressed serious concerns regarding the risk/benefit ratio of bremelanotide with regards to the side effect of increased blood pressure. The FDA stated that they would consider alternate uses for bremelanotide, including as a treatment for individuals who do not respond to more established ED treatments. However, On May 13, 2008, Palatin Technologies announced it had "discontinued development of Bremelanotide for the treatment of male and female sexual dysfunction" while concurrently announcing plans to develop it as a treatment for hemorrhagic shock instead.[5] The company additionally announced intentions to focus its attention on another compound, PL-6983, that causes lower blood pressure in animal models.[6] Palatin has since re-initiated Bremelanotide studies for ED and FSD using a subcutaneous delivery method. On August 12, 2009, the company announced that in a double-blind study of 54 volunteers bremelanotide failed to evoke the hypertensive side effects seen with the nasal delivery system used in prior studies, concluding that "variability of uptake" inherent in intranasal administration of the drug resulted in "increases in blood pressure and gastrointestinal events...primarily related to high plasma levels in [only] a subset of patients" and that subcutaneous administration of the drug circumvented the potential for this side effect. It is now in discussions with the FDA to resume Human Phase 2 studies utilizing subcutaneous administration.[6]

Structure

Bremelanotide is a cyclic hepta-peptide lactam analog of alpha-melanocyte-stimulating hormone (alpha-MSH) that activates the melanocortin receptors MC3-R and MC4-R in the central nervous system. It has the amino acid sequence Ac-Nle-cyclo[Asp-His-D-Phe-Arg-Trp-Lys]-OH or cyclo-[Nle4, Asp5, D-Phe7, Lys10]alpha-MSH-(4-10). It is a metabolite of Melanotan II that lacks the C-terminal amide function.

See also

References

Cite error: Invalid <references> tag; parameter "group" is allowed only.

Use <references />, or <references group="..." />

External links

de:Bremelanotid

pl:Bremelanotid

pt:Bremelanotide
  1. Bremelanotide for Organ Protection and Related Indications, Palatin Technologies fact sheet. Retrieved on 2009-01-18.
  2. "Tanning drug may find new life as Viagra alternative". CNN. 1999. Retrieved 2007-09-16. 
  3. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  4. Vicki Mabrey (2006). "ABC News "The Business of Desire - Love Potion"" (HTML, Flash Video). ABC News. Retrieved 2009-01-24. 
  5. "Palatin Technologies announces new strategic objectives and reports third quarter 2008 financial results". Palatin Technologies press release. 2008. Retrieved 2008-08-21. 
  6. 6.0 6.1 "Palatin Technologies Announces New Strategic Objectives". Retrieved 2008-05-13.