Re-examining the safety profile of melanotan 2? (+ contrast with mt1)


2.5 Pharmacokinetics and metabolism
Apart from its binding to MC1R, afamelanotide binds weakly to MC3R and MC4R [50], which mainly are expressed in the gastrointestinal system and CNS, respectively. The inability of afamelanotide to penetrate the blood--brain barrier after systemic application prevents the activation of these receptors [51,52], and no anorexia or sexual stimulation is reported after application of therapeutic doses.
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Again, who knows, really?

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Reference 51:


Is a laughable read.

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Reference 52:


Carries little actual information on the claim.
 
www.ncbi.nlm.nih.gov

Novel approaches to the design of bioavailable melanotropins

The melanocortin system is a primordial and critical system for survival, involved in a wide variety of physiological functions. It includes melanocortin receptors (MCRs) and melanotropin ligands (MCLs). MCRs are important drug targets that can regulate ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

MT-I, which has limited ability to pass through the blood–brain barrier [25], cyclized peptides have their unique advantage of passing through the blood–brain barrier and exert direct actions in the central nervous system.
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Ref 25:

pubmed.ncbi.nlm.nih.gov

Fluorine-18-labeled [Nle4,D-Phe7]-alpha-MSH, an alpha-melanocyte stimulating hormone analogue - PubMed

The alpha-melanocyte stimulating hormone (alpha-MSH) analogue [Nle4,D-Phe7]-alpha-MSH was labeled with 18F using N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB) in > 80% radiochemical yield. The IC50 values of [Nle4,D-Phe7]-alpha-MSH and para-fluorobenzoyl-[Nle4, D-Phe7]-alpha-MSH ([Nle4,D-Phe7, …
pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov

I couldn't locate this claim in this paper.
 
super interesting thread even if hard to add anything, just keep it going

have you tried mt-1? what are the major differences? Deffo looking for a source when I finish my mt-2 vials. All the mole growing stuff seems toxic as f but I pretty much love the tanning effect
 
Some comprehensive thoughts on mt1 versus mt2 comparison from reddit:



Again referencing mt2 as hitting a lot of receptors with effects science has not explored or confirmed.
 
I haven't used mt1 but can definitely testify that mt2 isn't very specific in terms of receptor affinity. I haven't received any psychological impact but other forms of melanocortan receptor activation have been present such as the sexual arousal along with blood glucose changes.
 

Afamelanotide: Uses, Interactions, Mechanism of Action | DrugBank Online

Afamelanotide is an injectable subcutaneous implant used to mitigate phototoxicity secondary to erythropoietic protoporphyria (EPP).
go.drugbank.com go.drugbank.com

Metabolism

Details regarding the metabolism and metabolites of afamelanotide are sparse. The drug is more resistant to degradation by serum and proteolytic enzymes than its endogenous counterpart, α-MSH, but presumably undergoes a relatively rapid hydrolysis given its short half-life.4,10 It has been suggested that afamelanotide may be degraded in the same manner as α-MSH but at a much slower rate, or may instead be degraded intracellularly via endocytosis or non-specific proteases
 
To at least draw comparison between melanotan and something similar.

There is much more data on the FDA approved Bremelanotide (PT-141):


A notorious (of sorts) case of anhedonia that required ECT to resolve posted somewhere, probably reddit.

No mention of depression/anxiety responses in clinical trials.

ijms-24-12152-g006.png
 
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I'm trying to figure out obviously, if I'll tolerate mt1 better than mt2?

For one, it's speculated that mt1 doesn't cross the blood brain barrier, at least to the same extent at mt2, as the molecule is bigger.

Perhaps this would preclude psychiatric/auditory symptoms like tinnitus (theorized to originate in the lymbic system), and depression/anxiety.

Though - clinical trials report this as being "uncommon" side effects.
 
The company having acquired the patent for the original melanotan 1, renamed themselves to "Clinuvel", have released this report:


Apparently claiming mt1 could assist in recovery of photodamaged DNA/cells.

It's obviously not an independent report, and clinuvel are, I would imagine, attempting to gain traction for the licensure of "Scenesse", the brand name for mt1.

This has been approved in Europe anyways, I think the US also, for treating the rare skin condition EPP;

It's listed on the national medicines regulatory agency website here at least.

Interesting read.
 
Early Clinical Results

Relevant to the release of the CUV151 results are the findings from an early photoprotective program conducted in healthy volunteers which looked at the induction of sunburn cells (apoptotic cells), MED, and DNA damage following the administration of an aqueous injectable solution of afamelanotide and, later, an early implant formulation. The earlier study (EP002) published as Barnetson et al (2006) showed that MED significantly increased after two months of discontinuous treatment for those individuals receiving afamelanotide compared to untreated volunteers, and a significant reduction of sunburn cells as well as reduction in thymine dimers (a form of CPD) after 90 days (with a greater reduction seen in fair skin types).

minimal erythema dose = (MED)
 
Funnily, their website, clinuvel.com, lists the following as their R&D objectives:

SCENESSE® (afamelanotide 16mg implant)
First-in-class photoprotective and repigmentation drug with EMA, US FDA and Australian TGA approvals for rare disease EPP. Phase IIb trial completed in Singapore for vitiligo. Trial programs for stroke and DNA Repair.
CUV9900
An alpha-Melanocyte Stimulating Hormone (alpha-MSH) analogue in early development.
Parvysmelanotide (VLRX001)
An alpha-Melanocyte Stimulating Hormone (alpha-MSH) analogue in early development.
PRÉNUMBRA®
PRÉNUMBRA® is a liquid (non-solid) injectable formulation of afamelanotide designed for administration by a healthcare professional and intended to provide a flexible dose of afamelanotide, a synthetic analogue of natural α-melanocyte stimulating hormone.
NEURACTHEL® (ACTH)
Translating its expertise in melanocortins and formulation development, CLINUVEL is commercialising NEURACTHEL® (adrenocorticotropic hormone; ACTH) in multiple dosage forms for patients in need of medical treatment. ACTH is a naturally occurring hormone which plays an important role in the production of cortisol, enabling the combat of stress and regulation of immune responses, maintenance of blood pressure, moderation of blood sugar, and regulation of metabolism.

I find it surprising mt2 isn't listed on there, as it's the most popular?
 
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www.imperial.ac.uk

Chemistry busts harmful tanning products for the BBC | Imperial News | Imperial College London

The Agilent Measurement Suite appeared as an expert witness in a recent BBC investigation.
www.imperial.ac.uk www.imperial.ac.uk

The BBC journalists also wanted to test claims that the tanning products were 99% pure. One look at the LC-MS trace is enough to dismiss that idea. “You can see over 100 other peaks in the separation, so you can say that there are many other components in the sample,” Professor Cass says. “But it’s another matter to say exactly what those components are.”

readout from chemical analysis


LC-MS results from seven samples. The large peak on the left is the melanotan, while the other peaks are unidentified impurities and contaminants.


Yikes.
 
That´s not funny, but MT2 is so powerful working at 50mcg that the contaminants should be mostly indiscernible

In any case Im all for MT-1. I cant stand the Mt2 nausea and the moles anymore
 
Hexagon Sun said:
That´s not funny, but MT2 is so powerful working at 50mcg that the contaminants should be mostly indiscernible

In any case Im all for MT-1. I cant stand the Mt2 nausea and the moles anymore
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Have you been using mt1?

And did you mean to say 500 mcg, not 50?

I'm super fair and never found those low doses effective, though some swear by them.
 
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