Download MSH therapies

Melanocyte-stim. hormone
= MSH
= peptide hormone produced by
1.  cells in the intermediate lobe of the pituitary gland => stimulates the
production & release of melanin (melanogenesis) by melanocytes in
skin & hair
2.  a subpopulation of neurons in the arcuate nucleus of the hypothalamus
=> MSH released into the brain by these neurons has effects on
appetite & sexual arousal.
MSH originates
Pituitary
gland
MSH
MSH
Arcuate nucleus
Proopiomelanocortin derivatives
Proopiomelanocortin
Anterior
pituitary
gland
γ-MSH
Interme
diate
lobe
cleavage
ACTH
α-MSH
β-lipotropin
γ-lipotropin β-endorphin
β-MSH
MSH originates
MSH
MSH
Dominating
Skin color
Hair color
Sex
AGING
=> MSH
Seasonal rhythm of alpha-MSH
only for skin types I and II
REPORT: a seasonal rhythm of alpha-MSH + raised levels of alpha-MSH
in summer & low levels in winter. in 20- to 40-year-old subjects of
•  skin type I (light color of skin and eyes, red hair, no tanning after sun
exposure)
•  skin type II (light color of skin, eyes, & hair, rare tanning)
With increasing age of the subjects =>the seasonal rhythm seems to be
lost.
•  In subjects with skin type III (light skin, brown eyes and black hair,
strong pigmentation after sun exposure) alpha-MSH shows only
insignificant variations over the whole year.
•  A seasonal rhythm of ACTH could not be demonstrated. A diurnal
rhythm could be seen for ACTH, but not for alpha-MSH.
CCL: the seasonal rhythm of alpha-MSH is controlled bya varying UV
exposure of the integument which is different over the whole year.
Altmeyer P, Stöhr L, Holzmann H. Seasonal rhythm of the plasma level of
alpha-melanocyte stimulating hormone. J Invest Dermatol. 1986 Apr;86(4):
454-6.
Disappearance w/age of the seasonal rhythm
in alpha-MSH for skin types I and II
REPORT: a seasonal rhythm of alpha-MSH + raised levels of alpha-MSH
in summer & low levels in winter. in 20- to 40-year-old subjects of
•  skin type I (light color of skin and eyes, red hair, no tanning after sun
exposure)
•  skin type II (light color of skin, eyes, & hair, rare tanning)
With increasing age of the subjects =>the seasonal rhythm seems to be
lost.
•  In subjects with skin type III (light skin, brown eyes and black hair,
strong pigmentation after sun exposure) alpha-MSH shows only
insignificant variations over the whole year.
•  A seasonal rhythm of ACTH could not be demonstrated. A diurnal
rhythm could be seen for ACTH, but not for alpha-MSH.
CCL: the seasonal rhythm of alpha-MSH is controlled bya varying UV
exposure of the integument which is different over the whole year.
Altmeyer P, Stöhr L, Holzmann H. Seasonal rhythm of the plasma level of
alpha-melanocyte stimulating hormone. J Invest Dermatol. 1986 Apr;86(4):
454-6.
MSH
darkens
the skin
Higher beta-MSH in
chronically hyperpigmented patients
REPORT:
• 
In serum of chronically hyperpigmented patients +
Addison's disease, Cushing's disease (after bilateral
adrenalectomy), & the ectopic ACTH syndrome => serum
beta-MSH conc. of 500-6000 pg/ml were found.
• 
The degree of clinical hyperpigmentation => well corr.
w/ the level of beta-MSH in the plasma.
•  serum beta-MSH of normal subjects : < 90 pg/ml.
• 
it was found that most of the biologic MSH activity of
the plasma & tissues could be accounted for by betaMSH
Abe K, Nicholson WE, Liddle GW, Island DP, Orth DN. Radioimmunoassay of betaMSH in human plasma and tissues. J Clin Invest. 1967 Oct;46(10):1609-16.
MSH => stim. melanogenesis
in the skin
MSH
The melanoblasts
=> differentiate into
melanocytes in the skin
=> produce
melanin pigment
= granules
=> incorporated into
surrounding
keratinocytes
⇒ ↑ synthesis
of melanin
α-MSH analogue (MT1)
=> ↑ melanin density in Caucasians
SUBJECTS: 77 Caucasian individuals
TREATMENT: MELANOTAN (MC1 receptor agonist) (vs placebo)
• 
sign. ↑ melanin density (p<0.001)
• 
sign. ↑ the melanin density to a greater extent in individuals
carrying the variant alleles MC1R genotypes
•  Val60Leu & Val92Met
•  Asp84Glu
•  Arg142His, Arg151Cys, & Arg160Trp than in individuals
with no variant alleles.
CCL: MELANOTAN
=> effectively ↑ melanin content of skin in those persons + MC1R
variant alleles = those most in need of photoprotection.
Fitzgerald LM, Fryer JL, Dwyer T, Humphrey SM. Effect of MELANOTAN, [Nle(4), D-Phe(7)]-alphaMSH, on melanin synthesis in humans with MC1R variant alleles. Peptides. 2006 Feb;27(2):388-94
Genetic Epidemiology Unit, Menzies Research Institute, Hobart, Tasmania 7001, Australia
Melanotan I => ↑ sun tanning
SUBJECTS: 4 subjects + melanotan-1 (MT-1, or [Nle(4)-DPhe(7)]alpha-MSH) (0.08 mg/kg/day subcutaneously)
↑↑ doses: 5.6 mg/day for 70 kg/154 pounds person
vs
4 control subjects to injections of isotonic sodium chloride
(9%)solution for 10 days, followed by neck irradiation with 3
times the minimal erythema dose (MED) of UV-B light.
RESULTS: Tanning in the study =>
achieved in 3 of 4 subjects + MT-1, & these subjects had 47%
fewer sunburn cells at the irradiated neck site.
•  no pathologic findings at any UV-B or sun-exposed sites in any
subject. Toxic effects due to MT-1 = minor = of nausea &
transient facial flushing.
Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Alberts DS. Effects of a superpotent
melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Arch
Dermatol. 2004 Jul;140(7):827-35.
Before
2 to 4 weeks of
MSH –derivative
treatment
Before
2 to 4 weeks
after
Stronger body scent
Brown to black skin
in a Caucasian subject
Even the doll Barbie uses
melanotan II
MSH Effects
or Cortisol deficiency
Darkening
of the armpits
MSH Effects
or Cortisol deficiency
Darkening
of the armpits
MSH effects
or Cortisol Deficiency
Brown creases
MSH - ACTH Effects
or Cortisol deficiency
Darkening
of the distal end
of the nails
MSH or ACTH effects
or Cortisol Deficiency
Darkening of skin
Browning of distal end
of the nails
MSH Effects
or Cortisol deficiency
Darkening
of the armpits
Protect
against
sunburn
Melanotan I => ↓ sunburns
SUBJECTS: Irradiation with 3 times the minimal erythema dose (MED) of UV-B
light.
2nd study (n = 12 subjects), + melanotan-1 (MT-1) => ↑ to 0.16 mg/kg/day for
10 days + UV-B radiation (0.25-0.75MED) on buttock site for 5 days during
(n = 7) or after (n=5) MT-1
3rd study randomized 8 subjects to 3 to 5 days of sunlight to half of the back or
to sunlight plus 0.16 mg/kg of MT-1 for 5 days per week for 4weeks.
RESULTS: Tanning in the first study => achieved in 3 of 4 subjects + MT-1
•  More skin sites darkened with the higher dose of MT-1 in the
second study.
•  In the third study, there was significantly enhanced tanning of
the back in the MT-1 group, and this was maintained at least
3 weeks longer than the tanning in the sunlight-only controls,
who required 50% more sun-exposure time for equivalent
tanning.
Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Alberts DS. Effects of a superpotent
melanotropic peptide in combination with solar UV radiation on tanning of the skin in human volunteers. Arch
Dermatol. 2004 Jul;140(7):827-35.
α-MSH analogue => ↑ melanin density &
↓ sunburn damage in Caucasian women
SUBJECTS: 65 Caucasian women
TREATMENT: potent synthetic melanotropin,[Nle4-D-Phe7]-α-MSH) in
subcut. Inj. into abdomen for 3x 10-day cycles over 3 months.
•  sign.↑ melanin density, in all [Nle4-D-Phe7]-α-MSH-treated subjects:
The highest ↑ in subjects + lowest baseline skin melanin levels
•  + 41% ↑ melanin in subjects + low minimal erythemal dose
(MED) skin (P < 0.0001) vs placebo) over 8 separate skin sites
•  only +12% (P <0.0001 vs placebo) in subjects + high-MED skin type
•  > -50 % ↓ epidermal sunburn cells <= 3 MED of UV radiation in
subjects + low baseline MED.
•  -59%Thymine dimer formation 59% (P = 0.002) in epidermal basal layer
CCL: alphMSH => ↓ some of the effects of UV radiation, the major
cause of skin cancer
Barnetson RS, Ooi TK, Zhuang L, Halliday GM, Reid CM, Walker PC, Humphrey SM, Kleinig MJ. [Nle4-D-Phe7]alpha-melanocyte-stimulating hormone significantly increased pigmentation and decreased UV damage in fairskinned Caucasian volunteers. J Invest Dermatol. 2006 Aug;126(8):1869-78 Department of Dermatology, Royal
Prince Alfred Hospital at the University of Sydney, Sydney, Australia. [email protected]
α-MSH or analogue => ↑ eumelanin,
↑ DNA repair, ↓ apoptosis, ↓ melanoma
MATERIAL: human melanocytes
TREATMENT: alpha-MSH
•  ↑ eumelanin synthesis,
•  ↓ apoptosis due to ↓ hydrogen peroxide generation
•  ↑ repair of DNA photoproducts
α -MSH analogue (melanocortin 1 receptor (MC1R) agonist)
•  ↑ activity of tyrosinase, thus melanogenesis
•  ↓ apoptosis & release of hydrogen peroxide
•  ↑ repair of DNA photoproducts in melanocytes exposed to UV radiation
•  Effects => ↓↓ abrogated by an analog of agouti signaling protein, the
physiological MC1R antagonist
•  Effects => Absent in melanocytes expressing loss-of-fn MC1R
CCL: Topical MSH analogs => prevent skin photocancer, esp. melanoma
Abdel-Malek ZA, Kadekaro AL, Kavanagh RJ, Todorovic A, Koikov LN, McNulty JC, Jackson PJ, Millhauser GL,
Schwemberger S, Babcock G, Haskell-Luevano C, Knittel JJ.Melanoma prevention strategy based on using
tetrapeptide alpha-MSH analogs that protect human melanocytes from UV-induced DNA damage and cytotoxicity.
FASEB J. 2006 Jul;20(9):1561-3 Department of Dermatology, University of Cincinnati College of Medicine, 231
Albert Sabin Way, Cincinnati, Ohio 45267-0592, USA. [email protected]
MSH-like
Preparations
=> Sun
protection
Brown under fluorescent lamps?
=> higher alpha-MSH & cortisol
REPORT: Fluorescent
rays =>
•  small wavy fluctuations of the plasma concentration of
alpha-MSH within normal ranges.
•  Some test persons revealed a steep increase of cortisol
values shortly after beginning of fluorescent lighting,
indicating that fluorescent rays may induce
endocrinological reactions.
Bartelt RN, Altmeyer P, Stöhr L, Gornik P, HOlzmann H. [Endocrinologic reactions
following exposure to fluorescent lamps] Z Hautkr. 1986 Feb 1;61(3):105-10.
For which skin-type is
MELANOTAN II suitable?
Evaluating the dose of Melanotan II:
for Sun Protection
My bodyweight in
kg
My Skin
Type is:
q 
q 
q 
q 
Skin Type 1
Skin Type 2
Skin Type 3
Skin Type 4
I want to: q  Tan slowly
q  Tan fast
q  Tan very fast
http://www.nasaltan-uk.com
Melanotan 1 & Melanotan 2:
Differences
Although Melanotan 1 & Melanotan 2 are similar in name
They possess different biological properties
=> Melanotan 2 =>
• 
an increase in libido
• 
weight loss properties not found in melanotan I.
MELANOTAN II => Skin type 1
Celtic type
reddish or very fair hair
Visible Signs:
- very bright skin color
- reddish or very fair hair
- blue, green or light grey eyes
- Freckles
- very bright nipples
- does not become brown
- very often sunburn
85% of the users become brown with Melanotan II
Protection time against solar irradiation 10 min. => with Melanotan II 20 - 30 min.
MELANOTAN II => Skin type 2
Northern type
blond or tan hair
Visible Signs:
- bright skin color
- blond or tan hair
- blue, grey or green eyes
- often freckles
- moderately brown nipples
- becomes only slowly brown
- often sunburn
95% of the users become brown with Melanotan II
Protection time against solar irradiation 10 - 20min. => Melanotan II: 20 - 60 min.
MELANOTAN II => Skin type 3
Mixing
type
- deep brown or tan hair
-  sometimes also blond or black hair
Visible Signs:
- middle skin color
- deep brown or tan
sometimes also blond or black hair
- brown (blue, green or dreads) eyes
- hardly freckles
- moderately pigmented nipples
- becomes relatively quickly brown
- sometimes sunburn
100% of the users become brown with Melanotan II
Protection time against solar irradiation 20 - 30 min.=> Melanotan II: 40 - 120 min.
MELANOTAN II => Skin type 4
Mediterranean type
Visible Signs:
- brownish or olive-coloured skin
also in unbrowned state
- brown eyes brown or black hair
- no freckles
- dark nipples
- becomes quickly brown
- seldom sunburn
100% of the users become brown with Melanotan II
Protection time against solar irradiation 30 min.=> Melanotan II: 60 - 180 min.
For which skin-type is
MELANOTAN II suitable?
Skin type 1 Celtic type
85% of the users become
brown
Skin type 2 Northern type
95% of the users become brown
Skin type 3 Mixing type
100% of the users
become brown
Skin type 4 Mediterranean type
Skin type 5 African type
100% of the users become brown
100% of the users are brown/black
http://www.nasaltan-uk.com
Synergy
MSH + Testo
=> Sebum secretion
Alpha-MSH => act synergistically w/
testo to stim. => sebaceous, prostate & seminal
vesicles in hypophys-ectomized-castrated rats
The sebaceous glands differed from the other 3 organs
in that alpha-MSH not only acted synergistically, but
also had a significant effect which was independent
of the presence of exogenous testosterone.
The response of the brown adipose tissue to testerone,
considerably
reduced by hypophysectomy, was not restored by alphaMSH. The Harderian & lachrymal glands were also
pituitary-dependent and their weights in
hypophysectomized-castrated rats were not
restored by alpha-MSH.
Ebling FJ, Ebling E, Randall V, Skinner J. The synergistic action of alpha-melanocyte-stimulating
hormone and testosterone of the sebaceous, prostate, preputial, Harderian and lachrymal glands,
seminal vesicles and brown adipose tissue in the hypophysectomized-castrated rat. J Endocrinol.
1975 Sep;66(3):407-12.
Testo & alpha-MSH => synergistic effect on sebum
secretion & on dermal & preputial gland lipogenesis
•  SUBJECTS: hypophysectomized rats.
•  RESULTS: Hypophysectomy reduced sebumsecretion, sebaceous and preputial gland
size, and dermal and preputial glandlipogenesis. The greatest effects were seen on the
biosynthesis of wax esters andsqualene. Testosterone propionate (TP) increased
sebum secretion, sebaceous glandvolume and preputial gland weight and lipogenic
activity, but had no significant effect on the pattern of lipid labelling. alpha-MSH had no
effect on sebaceous orpreputial gland size, but increased sebum secretion and dermal
lipogenesis,especially wax ester biosynthesis. When given together TP and alphaMSH had asynergistic effect on sebum secretion and on dermal and preputial
glandlipogenesis, and the pattern of lipid labelling was shifted towards normal.
TPand alpha-MSH also showed synergism in increasing preputial gland weight,
buttogether they had no greater effect on sebaceous gland volume than that
achieved with TP alone. These results suggest that TP and alpha-MSH have different
actionson the sebaceous glands with alpha-MSH acting predominantly on lipogenesis
and TPon cellualr proliferation and turnover leading to an increase in gland
size.Preputial glands differ from cutaneous sebaceous glands in their response
toalpha-MSH and androgen which could be a reflection of their more
specilizedfunction.
Thody AJ, Cooper MF, Bowden PE, Meddis D, Shuster S. Effect of alpha-melanocyte-stimulating hormone and
testosterone on cutaneous and modified sebaceous glands in the rat. J Endocrinol. 1976 Dec;71(3):279-88..
MSH
Deficiency:
Complaints
MSH deficiency complaints
Great difficulties to sun tan
MSH deficiency complaints
Easy sunburn
Skin damage
by sun
exposure
MSH Deficiency complaint
Gray hair
MSH deficiency complaints
in men
Erectile dysfunction
MSH deficiency complaints
in women
Low sexual sensitivity & no or poor orgasm
Whe MSH deficiency is
not treated in women …
Because
sex without
increased
sexual
sensitivity
&
orgasms
is not funny ..
Whe MSH deficiency is
not treated in men &women …
I think you haven’t
had intercourse
since a long
moment!
Normal
sperm
Your
sperm
MSH
Deficiency:
Physical signs
MSH deficiency signs
Flat, non
curling hair
Gray hair
White,
Caucasian skin
Blue iris
MSH deficiency signs
Inflammed eyes
Blue iris
inflammation
MSH deficiency signs
Sunburned skin
Overweight
obese bod
MSH deficiency sign
Overweight body u to massive obesity
MSH
Deficiency:
Lab test
Lab test:
Serum α-MSH
Level
only in
research labs
Alpha-MSH = major alpha-MSH-like
immunoreactive peptide
present in human blood
REPORT:
20 patients with non-endocrine diseases =>
alpha-MSH was the major alpha-MSH-like immunoreactive
peptide present in human blood with a level of 2-5 pg/ml.
(median 2.0 pg/ml, n = 11).
Des-acetyl alpha-MSH was present in human blood in only a
minor quantity.
Kortlandt W, De Rotte AA, Arts CJ, Croughs RJ, Thijssen JH. Characterization of
alpha-MSH-like immunoreactivity in human plasma. Acta Endocrinol (Copenh). 1986
Oct;113(2):175-80.
MSH
Treatment
Diet
=> ↑ MSH
Fasting => lowers alpha-MSH
in humans
Alcohol => reduces alpha-MSH
SUBJECTS: lactating rats
ACUTE ALCOHOL: inhibits the release of alpha-MSH
granules in cells of the intermediate lobe and PRL
granules from PRL-cells in the pars distalis by suckling
as observed at in electron microscopic observations.
CCL: acute administration of alcohol to lactating rats
prevents both changes and consequently inhibits the
suckling-induced PRL surge.
Mizuno W, Hirano N, Shiino M. The effect of alcohol injection on suckling-induced
PRL and alpha-MSH release in lactating rats. Alcohol. 1995 Jan-Feb;12(1):7-14.
Department of Anatomy, Wakayama Medical College, Wakayama City, Japan
Physical
Exercise
=> ↑ MSH
Physical exercise
=> ↑ Gamma MSH
SUBJECTS 10 young healthy subjects => 3 diff. stages of
physical activity
LEVELS:
• 
Serum gamma 2-MSH-LI (like immunoreactivity)
increased from 1009 pmol l-1 at supine rest to 1281 pmol
l-1 after 10 min walking (P < 0.05), => remained at this
increased level also after a consecutive further increase
of physical activity (4’ stair rush), 1293 +/- 87 pmol l-1 (P
< 0.05 vs. at rest).
• 
The increase in serum gamma 2-MSH-LI levels
Knudtzon
J. Alpha-melanocyte
stimulating
hormone increases
preceded
the elevation
of the venous
plasma plasma levels of
glucagon and insulin
noradrenaline
levelin rabbits. Life Sci. 1984 Feb 6;34(6):547-54.
MSH
Medications
MSH-like
Preparations
Alpha-MSH: structure
Molecular Formula:
Formula Weight:
C77H108N20O20S
1665.87
Different MSH’s: amino acid sequences
Amino acid
sequence
α-MSH
(medium: 14 AA)
β-MSH
(longer; 22 AA)
γ-MSH
(shorter; 12 AA)
Anti-inflammatory
Melanine- Sexuality
production stimulat.
Ac-Ser-Tyr-Ser-MetGlu-His-Phe-Arg-TrpGly-Lys-Pro-Val
+
++
+
Ala-Glu-Lys-Lys-Asp-Glu-GlyPro-Tyr-Arg-Met-Glu-His-PheArg-Trp-Gly-Ser-Pro-Pro-LysAsp
?
+
?
Tyr-Val-Met-Gly-HisPhe-Arg-Trp-Asp-ArgPhe-Gly
+
+
?
Synthetic derivatives
Melanocortan I
afamelanotide
13 AA
Melanocortan II 7 AA
Bremelanotide
formerly PT-141 –
developed from
melanotan II
7 AA Ac-Nle-cyclo [AspHis-D-Phe-Arg-Trp-Lys]-OH
or cyclo-[Nle4, Asp5, DPhe7, Lys10]alpha-MSH(4-10). It is a metabolite of
Melanotan II that lacks the
C-terminal amide function
?
+++
No
+
+++
+++
Concerns of
increased
blood
pressure
+++
What are the drugs Melanotan &
Melanotan II?
Melanotan & Melanotan II = synthetic versions of melanocyte stimulating
hormone that were created, synthesized and developed at The
University of Arizona and the Arizona Cancer Center.
Melanotan = a linear, full length peptide (containing all 13 amino acids).
Melanotan II = shortened, circular version of the same peptide. Both
Melanotan & Melanotan II => sunless tanning capabilities but because
Melanotan II had libido enhancement & spontaneous erections as side
effects => now being developed as a sexual & erectile dysfunction drug.
Note: To be particularly clear regarding Melanotan (due to previous
incorrect news reports) it should be noted that it does not cause
sexual arousal nor have erectile effects. These aspects are only found
in the drugs Melanotan II and bremelanotide.
Wessells H, Levine N, Hadley ME, Dorr R, Hruby V. Melanocortin receptor agonists, penile erection, a
sexual motivation: human studies with Melanotan II. Int J Impot Res. 2000 Oct;12 Suppl 4:S74-9.
Melanotan I: Afamelanotide
Molecular
Formula
Molecular
Weight
C78H111N21O19
1646.85
Melanotan II: structure
Melanotan I & II: structure
Melanotan I
Melanotan II
Cyclic structure
Melanotan I & II: structure
Melanotan I
Melanotan II
Melanotan I & II: Differences
Although Melanotan 1 & Melanotan 2 are similar in name they
possess different biological properties
Melanotan 2 causes
1.  an increase in libido
2.  weight loss
properties not found in the first version.
Impossible d'afficher l'image liée. Le fichier a peut-être été déplacé, renommé ou supprimé. Vérifiez que la liaison pointe vers le fichier et l'emplacement corrects.
MELANOTAN II PACKAGE
NASALTAN (Melanotan II)
the first Sun Protection Nose Spray
1 x Nose spray (violet glass)
Ingr. = 10mg Melanotan II per bottle.
3 x Nose spray (violet glass)
Ingr. Melanotan3 PLUS (10mg)
per bottle. Individual spray
dosage and instruction Leaflet
Usage: 3,5-4 ml depending on dosage
http://www.nasaltan-uk.com
Melanotan II óBremelanotide :
Differences
Both equally increase in libido & sexual potency
but bremalenotide provide ± 50% less sun tan.
Bremelanotide: structure
= metabolite of Melanotan II that lacks the C-terminal amide function
Melanotan II
Bremelanotide
= metabolite of Melanotan II
C50H68N14O10
C-terminal amide function
No C-terminal
amide function
Bremelanotide: Functions
formerly PT-141
It functions by activating the melanocortin receptors MC1R
& MC4R, to
•  modulate inflammation
•  limiting ischemia.[1]
•  treat sexual dysfunction but this application was
discontinued in 2008, after concerns were raised over
adverse side effects of increased blood pressure
• 
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 => no 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
Impossible d'afficher l'image liée. Le fichier a peut-être été déplacé, renommé ou supprimé. Vérifiez que la liaison pointe vers le fichier et l'emplacement corrects.
Bremelanotide
Package includes 1 vial
(10mg ea.) of PT-141 and 1
bottle (10ml) of
bacteriostatic water
Nasal
Spray
Bottle 20ml
(Empty)
Part 2 of Phase IIa trials involving post-menopausal women was presented at the International
Society for the Study of Women's Sexual Health (ISSWSH) 2007 Annual Meeting.
Melanotan I:
Afamelanotide
Molecular Formula
C78H111N21O19
Molecular Weight
1646.85
1
C50H69N15O9
1024.18
4
Molecular F
Molecular W
5
6
3b
3
Melanotan II:
3
3b
6
2
1
amide
2
Bremelanotide:
5
4
Molecular F
Molecular W
6
C50H69N14O10
1025.2
2
OH
1
lacks the C-terminal amide function
3b
PL-6983: The New Bremelanotide that
reduces BP
The PL-6983 compound is a new version of
Bremelanotide, a treatment for Female Sexual
Arousal Disorder and Erectile Dysfunction, in
development by Palatin Technologies.
SUBJECTS: animal subjects,
TREATMENT: PL-6983
•  increased sexual activity
• 
sign. lower increases in blood pressure than
was seen with Bremelanotide,
CCL: heightened blood pressure is the concern
cited by the FDA for not approving
Bremelanotide to treat Erectile Dysfunction.
Phase 1 Clinical Trials for this male and female
libido enhancing drug will begin in the near
future and it may eventually become the first
true aphrodisiac available to the public...
Melanotan
II
Bremelanotide
MSH-like
Preparations
=> Where
to buy?
Where to buy Melanotan II?
Where to buy Melanotan I
Melanotan I 10mg
3 vials = £90.00
Melanotan II 10 mg
3 vials =£80.00
Where to buy Melanotan II?
Melanotan II 10 mg
Melanotan II 10 mg
5 vials
1 vial = ±30 euros
Where to buy Melanotan II?
Melanotan II 10 mg
10mg Vial of Melanotan 2 premixed
+ 1ml of bacteriostatic fluid
+ 10 Syringes.
1 vials = 47$ = 31.2 euros
Melanotan II 10 mg
30mg Vials of Melanotan 2 (not
premixed)
+ 3ml of bacteriostatic fluid
+ 30 Syringes.
3 vials = 120$ = 81.6
euros
Where to buy Bremelanotide?
Melanotan II 10 mg
10mg vial of Bremelanotide
+ 10 ml of bacteriostatic fluid
+ No fillers
1 vials = 45$ = 30 euros
Melanotan II 10 mg
10mg vial of Bremelanotide
+ 10 ml of bacteriostatic fluid
+ No fillers
3 vials = 115$ = 78 euros
MSH-like
Preparations
=> How to
inject?
Melanotan I & II: How to inject
The injection is given into the sub-cutaneous layer which includes
adipose tissue (fat), as in the figure below:
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.
http://www.muscletalk.co.uk
MSH-like
Preparations
=> Avoid
excess dosing
Melanotan I & II: Excessive
Doses proposed on INTERNET
Melanotan I
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.
http://www.muscletalk.co.uk
MSH-like
Preparations
=> Adverse
effects
1st long-term Side effect
= excessive skin tanning
Before
MII
Overdose
1st long-term Side effect
= 2 types of excess skin tanning
Before
↑↑dose
Beautiful black-brown
due to
• ↑ MII dose
• + sun exposure +++
Before
MII Overdose
or healthier more
protected skin?
Less attractive grey/
yellowish brown
due to
• ↑↑ MII dose
• Little or no sun exposure
2nd long-term disturbing Side effect =
excessive pigmented spots
Before
MII Overdose
Only ↑↑↑
darkening of
existing
pigmented
spots (cortisol
sufficiency)
Naevi and
hyperpigmented
spots become
darker
↑↑↑ appearance
of new
pigmented spots
(sign of cortisol
deficiency)
New
hyperpgimented
spots may take
9 months to
disappear after
stopping the
treatment.
3rd disturbing Side effect =
Hypermigmentation of folds & greases
Pigmented
armpits
Signs of
cortisol
deficiency
Irregular
pigmentation
Pigmented
elbows
Brown
palmar folds
Darkening of the distal
end of the nails
MSH-derivative: Disturbing side effects?
Darkening/strong browning of the skin and naevi
=> The darkening is definitively only browning & not
a morbid change (cancer of the skin) of birthmarks.
http://www.nasaltan-uk.com
4th side effects: Bremelanotide, MI & MII
•  Nausea
• 
After taste
• 
Facial flushing
Nasal spray only:
•  Nasal congestion
(post-nasal drip)
Bremelanotide only
=>
•  ↑ blood pressure
MELANOTAN II: Disturbing side effects?
Feeling of sickness & un-wellness directly after the
application may occur
=> Appear only:
1.  If the body has no time to get gradually used to
MELANOTAN II or other MSH derivative
2.  In case of cortisol deficiency
http://www.nasaltan-uk.com
Bremelanotide: Adverse reactions
% of women
Melanotan I & II
References
Melanotan I & II: References -1
1. Hadley ME, Dorr RT
.Peptides. 2006 Apr;27(4):921-30. Epub 2006 Jan 18
Melanocortin peptide therapeutics: historical milestones, clinical studies and commercialization.
2. Hadley ME.
Peptides. 2005 Oct;26(10):1687-9
Discovery that a melanocortin regulates sexual functions in male and female humans.
3. Zheng H, Patterson LM, Phifer CB, Berthoud HR
Am J Physiol Regul Integr Comp Physiol. 2005 Jul;289(1):R247-58. Epub 2005 Mar 3
Brain stem melanocortinergic modulation of meal size and identification of hypothalamic POMC
projections
4. Grill HJ, Ginsberg AB, Seeley RJ, Kaplan JM
J Neurosci. 1998 Dec 1;18(23):10128-35
Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding
and body weight.
5. Shrestha YB, Wickwire K, Giraudo SQ
Neuroreport. 2004 Jun 7;15(8):1365-7
Action of MT-II on ghrelin-induced feeding in the paraventricular nucleus of the hypothalamus.
6. Trivedi P, Jiang M, Tamvakopoulos CC, Shen X, Yu H, Mock S, Fenyk-Melody J, Van der Ploeg
LH, Guan XM
Brain Res. 2003 Jul 11;977(2):221-30
Exploring the site of anorectic action of peripherally administered synthetic melanocortin peptide
MT-II in rats.
http://www.muscletalk.co.uk
Melanotan I & II: References -2
7. 
Dorr RT, Ertl G, Levine N, Brooks C, Bangert JL, Powell MB, Humphrey S, Alberts DS.
Arch Dermatol. 2004 Jul;140(7):827-35
Effects of a superpotent melanotropic peptide in combination with solar UV radiation on
tanning of the skin in human volunteers.
8.  Dorr RT, Dvorakova K, Brooks C, Lines R, Levine N, Schram K, Miketova P, Hruby V, Alberts
DS.
Photochem Photobiol. 2000 Oct;72(4):526-32
Increased eumelanin expression and tanning is induced by a superpotent melanotropin
[Nle4-D-Phe7]-alpha-MSH in humans.
9.  Barnetson RS, Ooi TK, Zhuang L, Halliday GM, Reid CM, Walker PC, Humphrey SM, Klienig
MJ
J Invest Dermatol. 2006 Aug;126(8):1869-78. Epub 2006 Jun 8
[Nle4-D-Phe7]-alpha-melanocyte-stimulating hormone significantly increased pigmentation
and decreased UV damage in fair-skinned Caucasian volunteers.
10.  Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME
Life Sci. 1996;58(20):1777-84
Evaluation of Melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I
clinical study
11.  Diamond LE, Earle, DC, Heiman JR, Rosen RC, Perelman MA, Harning R
J Sex Med. 2006 Jul;3(4):628-38.
An effect on the subjective sexual response in pre-menopausal women with sexual arousal
disorder by bremelanotide (PT-141), a melanocortin receptor agonist.
http://www.muscletalk.co.uk
Melanotan I & II: References -3
12.  Wessells H, Gralnek D, Dorr R, Hruby VJ, Hadley ME, Levine N
Urology. 2000 Oct 1;56(4):641-6.
Effect of an alpha-melanocyte stimulating hormone analog on penile erection and sexual
desire in men with organic erectile dysfunction.
13.  Wessells H, Fuciarelli K, Hansen J, Hadley ME, Hruby VJ, Hadley ME, Levine N
J Urol. 1998 Aug;160(2):389-93
Synthetic melanotropic peptide initiates erections in men with psychogenic erectile
dysfunction: double-blind, placebo controlled crossover study.
14.  Molinoff PB, Shadiack AM, Earle D, Diamond LE, Quon CY
Ann N Y Acad Sci. 2003 Jun;994:96-102.
PT-141: a melanocortin agonist for the treatment of sexual dysfunction.
15.  Wessels H, Hruby VJ, Hackett J, Han G, Balse-Srinivasan P, Vanderah TW
Ann N Y Acad Sci. 2003 Jun;994:90-5
MT-II induces penile erection via brain and spinal mechanisms.
http://www.muscletalk.co.uk
Bremelanotide: References
formerly PT-141
Diamond LE, Earle DC, Rosen RC, Willett MS, Molinoff PB. (2004). Double-blind,
placebo-controlled evaluation of the safety, pharmacokinetic properties and
pharmacodynamic effects of intranasal PT-141, a melanocortin receptor agonist, in
healthy males and patients with mild-to-moderate erectile dysfunction. Int J Impot
Res. 16:51-9.
Rosen RC, Diamond LE, Earle DC, Shadiack AM, Molinoff PB. (2004). Evaluation of
the safety, pharmacokinetics and pharmacodynamic effects of subcutaneously
administered PT-141, a melanocortin receptor agonist, in healthy male subjects and in
patients with an inadequate response to Viagra. Int J Impot Res. 16:135-42.
Diamond LE, Earle DC, Heiman JR, Rosen RC, Perelman MA, Harning R. (2006). An
effect on the subjective sexual response in premenopausal women with sexual
arousal disorder by bremelanotide (PT-141), a melanocortin receptor agonist. J Sex
Med. 3:628-38.
Nargund RP, Strack AM, Fong TM. (2006). Melanocortin-4 receptor (MC4R)
agonists for the treatment of obesity. J Med Chem. 49:4035-43.
Thank for
your attention:
Any questions?