Endymion, given that melanotan II is thought to actually moderate allergy and inflammatory reactions, how do you fit this into your theory?
 
I've attached a number of studies. Here's a quote from one:
"Therapeutic application of alpha-MSH ... may be a useful approach for the treatment of inflammatory, autoimmune, and allergic diseases in the future."
 
What are your thoughts on that?

Question for Endymion (and other Antihistamine users),
 
You said you used Melanotan for years and also have used anti-histamines to make the side effects go away.
 
At this point, how confident are you that antihistamines make all of the (possibly) allergic symptoms go away like flushing? I was hoping the flushing and other side effects were neurologically triggered. Have you done a lot of trials in which sometimes you use antihistamines and sometimes you don't and have you found that the symptoms are always there without antihistamines but  never there when you take them?
 

Not exactly where I was going with this ... what I am saying is that the IgE antibodies reside on the mast cells and basophils. When the supposed antigen "melanotan II" comes into contact with the antibodies, it causes these cells to degranulate and release histamine and serine proteases inducing the temporary inflammation.
 
However, some new research I've been exploring indicates that there may be a completely natural explanation for this inflammation. The a-MSH peptide serves as a signaling hormone (analogous to the key that starts the car). Human dermal mast cells express MC1R just as the familiar melanocyte cell does. So what happens when this receptor is activated on the mast cell?
 
According to one source ... Effects of Melanogenesis-Inducing Nitric Oxide and Histamine on the Production of Eumelanin and Pheomelanin in Cultured Human Melanocytes written by Michael W. Lassalle, Shigeru Igarashi, Minoru Sasaki, Kazumasa Wakamatsu, Shosuke Ito, and Toshio Horikoshi.
 
"Nitric oxide (NO) and histamine are also melanogenesis-stimulating factors that are released from cells surrounding melanocytes following ultraviolet (UV) irradiation. In this study, the effects of NO and histamine on the ratio of eumelanin and pheomelanin were examined in human melanocytes, and then compared with that of α-MSH. The amounts of eumelanin and pheomelanin were quantified using high-performance liquid chromatography analysis after oxidation and hydrolysis of melanin."
 
"Melanogenesis was induced by the addition of α-MSH, NO, or histamine to melanocytes. The amount of eumelanin production significantly increased with independent stimulation by these melanogenic factors, especially histamine, while that of pheomelanin significantly increased with α-MSH and NO, but only slightly with histamine. As a result, the ratio of eumelanin and pheomelanin increased significantly with the addition of NO or histamine. These results suggest that NO and histamine, as in the case of α-MSH, may contribute to UV-induced hyperpigmentation by enhancing eumelanogenesis."
 
My latest theory is that an overdose of Melanotan into the bloodstream causes a large release of histamine that is out of proportion with normal release levels when compared to that caused by UV irradiation. I'm not sure how fast histamine reforms inside the mast cells and basophils, but this could explain why repeated injections on a scheduled basis do not elicit the same response ... since the balance of histamine may have already been discharged. Consequently, after a significant period of time passes, the pool of histamine may be restored and the side-effect would then return upon activation of these cells.

Hey Endy, I have a feeling that the local increase in melanogenesys caused by histamines and NO has a lot to do with hyperpigmentation spots when taking melanotan II.  Althogh the pieces don't quite fit yet, I have a feeling histamines and/or NO may play a big role in locally oxidizing eumelanin in the absence of UV, hence causing hyperpig spots without UV.  Any thoughts?

Quote from Philatio on 07/01/07 at 00:29:36:

 
They could be increased hay fever symptoms (even though you may have never experienced any hay fever symptoms in your life, they could have been present but hardly noticeable). Suggest you try zyrtec as stated in the first post. I use it as well and my problems are completely gone.

So the critical question (the answer to which i may have missed above) is... does melanotan II cause individuals to produce IgE?  
 
And does melanotan-1 not?

Hi,
About a month ago I started using Melanotan II (first time user), and gradually worked up to a point where I was injecting 1mg/day, usually in my stomach, but also in my arm once/twice; it took about 2 weeks to get to that stage and for the 1st week or so at this level I had no problems, until about 5/6 days ago when I got an outbreak of hives on my stomach. The injection sites on my stomach also flared up - usually after injecting, I might have a little bump for 2-3 hours which would then vanish, however, they all reappeared and now you can see clearly every injection I have made for the last month, about 20 red dots around my stomach. Interestingly enough, the places where I injected on my arms didn't flare up. Since then I've reduced the amount I'm taking to .5mg/day and the hives are beginning to go. I used a negligible amount of bacteriostatic water; 1cc/10mg and injected once in the evening after eating. I also started taking an iodine supplement last Thursday, which may have had something to do with it, although I would be doubtful about that, as I am still taking them as usual. I didn't eat/come into contact with anything else out of the ordinary over the past week. I assume 1mg in one injection is just slightly too high for my body as I'm only 120lb, however, I have looked around and haven't seen anyone else reporting a similar reaction so it is possible that it's completely unrelated. In a few days I'm going to try raising my dose again and seeing if I have a similar response...

Hi, felt I had to report my experience on here.  Am extremely pale with tons of freckles.  Never had a tan before.  Took Melanotan II, 50mg at about 1mg a day, but made a few blunders with doses, so slightly more sometimes.  stopped taking it about 4/5 weeks ago and have only since noticed loads of white spots.  loads, like white freckles.  Had to have a blood test to do with something else, and my doctor (who does not know that I have taken this), is concerned that my renal blood count is low.  Not too sure I really understand what that means, but I believe its to do with the kidneys.  I am to have another blood test soon, but am sure its to do with this, and I have been having regular blood tests and was fine before.  I  remember reading about this on another forum.  Does anyone else remember this and if so could they post a link.  If this is the case then this could be quite dangerous for possibly a select few individuals.  Hopefully, for me it will be OK, but I will let you know

Wow,interesting stuff endi>you always have the most reliable info.thankyou very much>i am going to have to realy start gauging my sides ,seeing as I am strtiang to run melanotan II in a higher dosage range 2mgs a day for the next 2 weeks ( an experiment)I am going to have some zyrtec on hand for sure...
  Endi what is your opinion on people building a tolerance to melanotan II?On having to use higher doses to acheive the same results the longer we use it?
 Thanks for any info

Anyone having a general body itching reaction with cutaneous eruptions i.e. hives should at the very least purchase a supply of injectable epinephrine to have on hand in case of a moderate to severe allergic reaction syndrome.  It can be obtained from most vet supply houses here in the US & Canada and is not a prescription item.
 
"Epinephrine injection is used to treat life-threatening allergic reactions caused by insect bites, foods, medications, latex, and other causes. Symptoms of allergic reaction include wheezing, shortness of breath, low blood pressure, hives, itching, swelling, stomach cramps, diarrhea, and loss of bladder control. Epinephrine is in a class of medications called sympathomimetic agents. It works by relaxing the muscles in the airways and tightening the blood vessels.'
 
Be safe.
 
Our family keeps a bottle on hand at all times in the fridge in this age of fire ants and africanized bees.  It's the first thing they give you in the emergency room for allergic reaction care.