Bremelanotide (PT-141)

[Chris White]

Bremelanotide (PT-141)

http://en.wikipedia.org/wiki/Bremelanotide


From Wikipedia

Bremelanotide
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
Identifiers
CAS number    189691-06-3
ATC code     ?
PubChem    23725087
Chemical data
Formula    C50H68N14O10
Mol. mass    1025.2
SMILES    eMolecules & PubChem


Bremelanotide (pronounced /brɛ ˌmɛ læ noʊ ˈtаɪd/ bremelanotide-pronunciation.ogg bremelanotide (help·info)) (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 discontinued in 2008, after concerns were raised over adverse side effects of increased blood pressure.
Contents
[hide]

    * 1 Development
    * 2 Structure
    * 3 See also
    * 4 References
    * 5 External links

Development

Originally, the peptide Melanotan II, that bremelanotide was developed from, was tested 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 be 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 "has discontinued development of Bremelanotide for the treatment of male and female sexual dysfunction" however they concurrently announced 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]

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.

[Chris White]

Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response.

http://www.ncbi.nlm.nih.gov/pubmed/15833522?dopt=AbstractPlus

Palatin Technologies, Inc., Cranbury, New Jersey 08512, USA. ldiamond@palatin.com

OBJECTIVES: To evaluate the safety and pharmacodynamic effect of co-administration of subtherapeutic doses of PT-141, a cyclic heptapeptide melanocortin analogue, and sildenafil to patients with erectile dysfunction. METHODS: Nineteen patients with erectile dysfunction who were responders to either Viagra or Levitra by self-report were given 25 mg sildenafil and 7.5 mg intranasal PT-141, 25 mg sildenafil and an intranasal placebo spray, and a placebo tablet and an intranasal placebo spray in a randomized cross-over design. Erectile activity in response to two 30-minute episodes of visual sexual stimulation was assessed by RigiScan during a 6-hour postdose period. RESULTS: The erectile response induced by co-administration of PT-141 and sildenafil was significantly greater than the response elicited by administration of sildenafil alone. Co-administration of PT-141 and sildenafil was safe and well-tolerated and did not result in new adverse events or adverse events that were increased in frequency or severity compared with monotherapy. CONCLUSIONS: Co-administration of intranasal PT-141 and a phosphodiesterase type 5 inhibitor may constitute a treatment alternative for patients in whom higher doses of a single therapy are not effective or well tolerated.

PMID: 15833522 [PubMed - indexed for MEDLINE]

[Chris White]

Have to say, 1mg PT141 four hours in advance and a PED5 inhibitor (viagra, cialis or levitra) ~30min before....

[SacCat]

my experience with this product was great, using cialis with it was mind blowing and probably not something i will do again unless i was at a swing party that's for sure.. I can't remember the last time i was awakened 5 times during the night due to erections that would not go away..

[Chris White]

my experience with this product was great, using cialis with it was mind blowing and probably not something i will do again unless i was at a swing party that's for sure.. I can't remember the last time i was awakened 5 times during the night due to erections that would not go away..

How much cialis did you use Sac? 

[SacCat]

20mg cialis..

again to follow up..

sunday (remember i administered on friday night)  I'm still amorous, the wife reports the same, more of a, "hey, you up for it again?? " kind of feeling

So it will be interesting to see how the effects continue to wain, or rather if they diminish over the next few days..

[Chris White]

I had hopes for my 5mg intranasal experiment, maybe I will try 7.5 then 10mg next attempts

[sempainick]

Due to no real knowledge of the correct ratio of melanotan 11 & the water to be mixed in the nasal apray bottle I have put two 10 m bottles of melanotan 11 with 30 ml of water.

Any input? too much? too little? and how many sprays?

Thanks

[Chris White]

Due to no real knowledge of the correct ratio of melanotan 11 & the water to be mixed in the nasal apray bottle I have put two 10 m bottles of melanotan 11 with 30 ml of water.

Any input? too much? too little? and how many sprays?

Thanks

Sorry to say you may have overdone things.  If I am understanding correctly...you have put 20mg MT-II into 30ml of water? 

How did you go about this sempainick?  Did you reconstitute both vials with 1ml of bact water for injection then extract into the bulk of the water?  Or did you remove the plastic flip top, aluminum, and rubber stopper in order to move the raw materials?
The peptide will degrade and may or may not be salvageable at this point.  Were you looking to get a tan or experience the aphrodisiac?

[SacCat]

Co-administration of low doses of intranasal PT-141, a melanocortin receptor agonist, and sildenafil to men with erectile dysfunction results in an enhanced erectile response.

http://www.ncbi.nlm.nih.gov/pubmed/15833522?dopt=AbstractPlus

Palatin Technologies, Inc., Cranbury, New Jersey 08512, USA. ldiamond@palatin.com

OBJECTIVES: To evaluate the safety and pharmacodynamic effect of co-administration of subtherapeutic doses of PT-141, a cyclic heptapeptide melanocortin analogue, and sildenafil to patients with erectile dysfunction. METHODS: Nineteen patients with erectile dysfunction who were responders to either Viagra or Levitra by self-report were given 25 mg sildenafil and 7.5 mg intranasal PT-141, 25 mg sildenafil and an intranasal placebo spray, and a placebo tablet and an intranasal placebo spray in a randomized cross-over design. Erectile activity in response to two 30-minute episodes of visual sexual stimulation was assessed by RigiScan during a 6-hour postdose period. RESULTS: The erectile response induced by co-administration of PT-141 and sildenafil was significantly greater than the response elicited by administration of sildenafil alone. Co-administration of PT-141 and sildenafil was safe and well-tolerated and did not result in new adverse events or adverse events that were increased in frequency or severity compared with monotherapy. CONCLUSIONS: Co-administration of intranasal PT-141 and a phosphodiesterase type 5 inhibitor may constitute a treatment alternative for patients in whom higher doses of a single therapy are not effective or well tolerated.

PMID: 15833522 [PubMed - indexed for MEDLINE]

I don't know about the nasal, but i did an injection of 2mg of the product subq.. then took 20mg of cialis, and i couldn't go to sleep, even after sex with the wife 3 times over the coarse of the evening..

Thank goodness she did the product with me, or i don't think she could have kept up..

Does it work?? wow.. yes, and you will be glad the next day if you can sneak a nap in..

[sempainick]

what I did chris is put the 30 ml bact water into spray botle, took off tops of vials and put into bottle.

did 10 sprays into each nostral, I am not interested in the tan but the sexual stimulant. the result was pretty good.

Do you think the melanotan 11 is as good for the sexual stimulant as pt-141?

[Chris White]

Do you think the melanotan 11 is as good for the sexual stimulant as pt-141?

Absolutely, thanks for the update.  So the results were pretty good huh? 

How long after the sprays did it take to feel anything?  Did it last more than a day?

[sempainick]

it took two hours for full effect and lasted about 24 hours

[lee]

Newbies here. Recently decided to try the PT141 from TR (subQ). First dose me - 0.5mg and the wife - 1mg. Brem flush and a few hours later mild sensations in the nether regions for both of us. Not really the WOW we were looking for. A week later we tried 1mg for me and 2mg for the wife. Pretty much the same results. Anybody have any comments on dosage or ideas about why neither of us are getting that 20 years younger feeling?  A newbie suggested dosage plan along with anticipated results would really be helpful at this point. Any constructive input will be greatly appreciated.

[Chris White]

Newbies here. Recently decided to try the PT141 from TR (subQ). First dose me - 0.5mg and the wife - 1mg. Brem flush and a few hours later mild sensations in the nether regions for both of us. Not really the WOW we were looking for. A week later we tried 1mg for me and 2mg for the wife. Pretty much the same results. Anybody have any comments on dosage or ideas about why neither of us are getting that 20 years younger feeling?  A newbie suggested dosage plan along with anticipated results would really be helpful at this point. Any constructive input will be greatly appreciated.

Welcome lee.  Feel free to start a fresh thread to keep the focus and attn on you  

Include some more info on a new topic with details such as to why you took 50% the dose of your other half...typically it is flipped.  Approx age, weight, stress, body mass, timing and expectations could be other valuable details.  Look forward to hearing more!
The stuff is certainly something that doesnt work for everyone, every time...but once understood and dialed in it can effectively give those youth feelings