Thursday, May 8, 2014

Melanotan and Melanotan II


Melanotan  and Melanotan II  are both analogs of the alpha-melanocyte stimulating hormone (α-MSH) which is produced within the pituitary gland. Along with other melanocortins, they are responsible for various internal human functions including skin and hair pigmentation, appetite, libido and physical sexual arousal. Whilst these effects have been observed in both sexes, it is worth noting that increases in libido and sexual function are exclusive to Melanotan-II.

Prompted by ultraviolet (UV) exposure, α-MSH release consequently stimulates production of melanin from the melanocytes within the skin. Melanin, as I'm sure you are aware, is a brown pigment and responsible for the tanning of the skin. Simply put, more α-MSH means more melanin, resulting in greater skin pigmentation. Since bodybuilding is such an aesthetic pursuit, and with darker skin that accentuates muscularity, it's little wonder that these drugs are in such high demand.

Both Melanotan and Melanotan II have been shown in the clinical setting to increase pigmentation without exposure to UV, a feature that is also confirmed anecdotally by users that report tanning in areas of the body that would seldom see the light of day! However, the process of tanning is greatly expedited by UV exposure. It is worth noting that tanning effects may not be uniform throughout the skin. This is in part due to the half life and distribution of the drug itself, but primarily in response to the concentration of melanocytes within certain areas of the skin. Most will notice the greatest tanning effect on the face, arms, abdominal region. Interestingly, the genitals have one of the highest concentrations of melanocytes enabling these particular areas to respond very well to the peptide in conjunction with UV exposure.

Suggested Cycles/Uses

If you look hard enough out there, you will find some weird and wonderful dosaging schedules whereby the user calculates their daily dosage by multiplying their bodyweight by a cofactor. Perhaps this approach has been adopted since this has been the method employed in the ongoing clinical studies. Typically, this type of formula would suggest a dose of 1mg of Melanotan-II per day for someone weighing in at a mere 110lb (50kg). The cynical among us might be forgiven for thinking that these formulae are constructed by those with a personal interest in the sale of the product as I believe this to be more than necessary to achieve a great result. Indeed, there are many instances whereby users feel they have become too dark. While I have no problem with a bodyweight dosage scale in principle, I can't help thinking that it's not only unnecessary (particularly for the mathematically challenged), but also avoids the ability to gradually increase dosages from a relatively low level; something which I would advocate to assess individual tolerance levels to side effects, especially in the case of Melanotan-II.

Clinical trials to determine efficacy of the drugs have typically used dosages up to 0.21mg/kg daily for Melanotan (16mg for a 75kg (165lb) individual), and up to 0.03mg/kg daily for Melanotan II (2.25mg for a 75kg (165lb) individual). More typically however, trials have used the dosages of 0.16mg/kg (12mg) and 0.025mg/kg (1.875mg) respectively. At this level of dosage, one such study involving Melanotan indicated the following incidences of side effects from subjects:

  • Nausea 85%
  • Facial Flushing 75%
  • Fatigue 44%
  • Vomiting 26%
  • Injection site reactions 13%
  • Zero incidence of erections
  • No change in vital signs or haematological parameters, blood biochemistry (liver and renal function)

As is the case with any drug use, the user is ideally looking to minimise unwanted side effects, whilst still achieving an acceptable outcome. With this in mind, I would suggest that a tapering up of dosages is used in order to assess the individual's personal tolerance to the side effects.

Both Melanotan and Melanotan II can be used for extended periods, whereby there is an initial daily administration of perhaps 2-3 weeks or until desired level of pigmentation has been achieved, followed by a maintenance phase of two injections per week.

Melanotan:
Start with a dose of 1mg daily for the first two or three days and, if level of side effects permit, look to increase dosage by 0.25mg every day over the next several days until you reach a daily dosage of 2-3mg. This level should be adequate for most users, though some may wish to increase yet further, perhaps as high as 5mg daily in order to achieve a very deep tan. A maintenance phase as described above is then used.

Melanotan II:
Start with a dose of 0.25mg. If side effects (primarily nausea) are not proving troublesome, attempt to increase daily dosage by 0.25mg where possible, until you reach 1-1.5mg daily. Most have found that this level will yield a very pleasing result and I can't see much point in increasing too much further unless a very deep tan was desired. As with Melanotan, once the desired level of tanning is reached, a maintenance phase is used.

Administration
Both Melanotan and Melanotan II are currently supplied as white lyophilised powder contained in a sealed multi-use vial. The peptide is susceptible to temperature degradation and should be shipped preferably with an ice pack though contrary to popular belief, the rate of degradation is very slow (weeks) in its powder form, so there's no need to be alarmed if yours wasn't shipped in this manner or you are unable to collect your package from a depot for a day or two. Once delivered, the powder is best stored in a freezer, or refrigerated if this is not possible.

To prepare for injection, it must be reconstituted with bacteriostatic water. You may use anything between 1ml and 5ml of water for your vial. Dependant upon the amount of water used will determine the concentration of your solution. For example, a 10mg vial of Melanotan II mixed with 1ml of water will provide a solution of 10mg per 1ml (10mg/ml). This means that a 1mg dose will require a shot of 0.1ml. Bearing in mind that the recommended starting dose is 0.25mg, using the example above, the actual volume of the shot would be 0.025ml (¼ of 1 tenth of a ml). This is a very small volume and very difficult to accurately dose even with a 0.5ml insulin syringe. Therefore, at least until your dosages have increased, it is suggested that you use more water for your vial.

An example of a good solution would be to mix 10mg of Melanotan II powder with 4ml of bacteriostatic water. This now provides:

10mg/4ml or 1mg/0.4ml or 0.25mg/0.1ml

0.1ml can be accurately measured using a 0.5ml or 1ml syringe.

Obviously, as your dosages become higher, you may dilute subsequent vials with lower amounts of water to reduce the volume of each shot. I would recommend that when you are using a dosage of 1mg, you reconstitute the vial with 1ml or 2ml of water so that each shot will be 0.1ml or 0.2ml respectively.

The injection is given into the sub-cutaneous layer which includes adipose tissue (fat).

If you are using insulin syringes which have short needles, you will need to enter the skin at 90°. to the skin, otherwise you can inject as shown in the illustration above with a 29 or 30 gauge, 0.5" needle.

I would suggest that you use standard 1ml syringes to which you can interchange needles as required. By doing so, you are able to attach any gauge/length you want to reconstitute and draw the solution (I use a 25guage 1" needle). Once done, simply attach your suitable needle for the injection. Following the injection, ensure that you pull back the plunger a little to 'reclaim' the solution that is contained within the needle itself. The syringe/needle is then placed in the refridgerator for storage until your next injection is due whereby you will attach a brand new injection needle. This process is repeated until you have administered all of the solution in that particular syringe.

Alternatively, you may pre-load insulin syringes and refrigerate until needed. However, because they have non-detachable needles, this can be quite cumbersome as they require loading from the rear.

Instability of the peptide is a much greater issue once reconstituted so you don't want it sitting in the fridge for months on end. Ideally one 10mg vial of Melanotan-II could be shared by two people (each having their own syringe/needles) so even during the maintenance phase of two injections per week of 1mg each; the longest it will be reconstituted for is 2.5 weeks.

Example of How to Dose Melanotan II

Draw 2ml of bacteriostatic water into the vial
On an insulin needle, start at 0.06ml (up to 6 little notches on the needle only – see diagram)
If this is ok then increase to 0.1ml on the needle
Do not use more than 0.15ml
Start every 2-3 days, then reduce as you get darker
Stored in the fridge and discard after 3 weeks

Major Differences

Melanotan's peptide structure is very closely matched to that of our endogenously produced alpha-melanocyte stimulating hormone (α-MSH). It is a specific agonist of the melanocortin-1 receptor (MC-1R) which is primarily responsible for skin colour and is found on melanocyte cells.

Melanotan II on the other hand has a much shorter sequence of amino acids and because of this quite pronounced change in length and structure, is an agonist of the range of melanocortin receptors. Perhaps more importantly, binding at receptors other than MC-1R is far greater than that of Melanotan. This 'shotgun effect' agonism of the full spectrum of different melanocortin receptors results in some effects that are only witnessed from Melanotan-II. Most notably, increases in sexual arousal are due to Melanotan-II's activation of MC-3R and MC-4R.

Because the amino acid sequence is much shorter in the case of Melanotan-II, there is therefore a much greater density of peptide chains than is present using Melanotan within a given set weight. Although the receptor binding affinity of Melanotan-II may not be quite as effective, there will be much more peptide chains than for Melanotan on a mg for mg basis so effectively you require much less in terms of milligram weight of Melanotan II to achieve similar results. This accounts for the wide difference in suggested dosages for each peptide and of course, makes Melanotan-II a much cheaper proposition.

                                     Effects / Side Effects
Melanotan                                                                         Melanotan II
Skin pigmentation                                                               Skin pigmentation
Nausea                                                                                 Nausea
Appetite suppression                                                           Appetite suppression
Flushing (esp. facial)                                                           Flushing (esp. facial)
Headache                                                                             Headache
Lethargy                                                                              Lethargy
Itching                                                                                 Itching
Dizziness                                                                             Dizziness
New mole appearance or darkening                                    New mole appearance or darkening
Hyperpigmentation                                                              Hyperpigmentation
White patches                                                                      White patches
Increased libido
Physical sexual arousal
Anaphylactic shock?

Of the above listed effects/side effects, it is worth bearing in mind that the prevalence and severity are witnessed to a greater degree from Melanotan II. Indeed, most will find Melanotan very comfortable to use, typically only experiencing minor nausea, appetite suppression and flushing.

Although side effects do become less troublesome with each administration of Melanotan or Melanotan-II, most users will experience at least some of the side effect to varying degrees, most commonly nausea, appetite suppression, facial flushing and dull headaches. These will typically become apparent within a few minutes of administration but can last for many hours. In the case of Melanotan-II, increases in libido are often seen in conjunction with outwardly physical signs of sexual arousal whereby the male user experiences prolonged periods of increased blood flow to the penis. This particular side effect does not diminish in severity over time and instances of occurrence are to be expected throughout the period of Melanotan-II use. As I'm sure you can appreciate, this aspect may prove embarrassing and perhaps quite uncomfortable, so I must stress again the importance of building dosage up gradually to assess personal tolerance and susceptibility.

Some users will notice the new appearance of freckles as these particular areas of skin have increased melanin. The good news is that as the tan is developed, the visual appearance of them will diminish, probably completely. Moles commonly become darker too as these are actually highly concentrated clusters of melanocytes. Both of these occurrences will reverse some time after discontinuation of the peptide and suntanning is ceased.

In addition to freckles and mole changes, there are fairly rare reports of a phenomenon called hyperpigmentation. This is typified by blotches of darkened skin, normally much larger than regular moles. Not all incidences of hyperpigmentation are attributable to increased melanocyte activity even though their appearance may only become apparent during melanocortin receptor agonism by Melanotan I or II. This condition is specifically referred to as diffuse hyperpigmentation, with many possible underlying causes or disorders including Addison's disease, haemochromatosis, hyperthyroidism and certain medications which may induce phototoxic reactions.

Previously unseen white spots or white patches of skin may also become apparent as the tan deepens. Again, this is not thought to occur as a direct result of using Melanotan, rather it merely uncovers the underlying condition. There are a range of actual causes. White spots (typically 2-5mm in size) may be the result of Idiopathic guttate hypomelanosis where there are reductions in the number of melanocytes and melanin in those particular areas. Larger white areas of skin may be due to Tinea versicolor which is a fungal infection caused by the yeast Malassezia furfur which is found on the skin and is not normally troublesome. Treatment would normally include an oral or topical anti-fungal though it may take many weeks for the skin tone to become consistent with surrounding areas.

It has been suggested that due to the greater difference of Melanotan-II to our own α-MSH, there is a greater chance of the body to view the peptide as a 'foreign body' and produce an allergic response. This could potentially trigger anaphylaxis, a potentially life threatening situation whereby large amounts of histamine are produced by the body which can lead to a host of effects including severe bronchoconstriction and rapid drops in blood pressure.

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