molonlabedoc
Member
Yea that entire era was wild. I really enjoyed Dr. Crysler as well. Sad end there.
Oral growth hormone enhancer MK-677 (ibutamoren)
- Thread starter Nelson Vergel
- Start date
BigTex
Well-Known Member
Yea, I was part of the board when it open as Dat and I posted on ProMuscle and American Muscle for a long time.Lots of good information there. ProMuscle still has some of the old stuff posted back when Swale (Dr. Crysler) posted. I was truly sorry to find out the truth behind DATs board, but I suspected it for about a year after he started pushing Tom's Peptides so heavily. Then to find out DAT was an attorney.
lunchbeast
Member
Care to share those?
Jed Dorsey
Active Member
BigTex
Well-Known Member
This shoudl explain the difference in natural GLP-1 foundint he gut and GLP-1 analogues
Semaglutide is a human GLP-1 analogue in clinical development for the treatment of T2D. It shares 94% structural homology with native human GLP-1, with three important modifications: amino-acid substitutions at position 8 (alanine to alpha-aminoisobutyric acid) and position 34 (lysine to arginine), and acylation of the lysine in position 26 with a spacer consisting of two 8-amino-3,6-dioxaoctanoic acid (ADO) moieties, a glutamic acid moiety, and a C-18 fatty di-acid side chain (Lau et al., 2015). The fatty di-acid side chain and spacer mediate strong binding with albumin, while the amino-acid substitution at position 34 limits the options for acylation to the one remaining lysine in the sequence; the substitution at position 8 reduces the susceptibility of semaglutide to degradation by DPP-4 (Lau et al., 2015). Together, these modifications prolong the t1/2 of semaglutide; a previous pharmacokinetic (PK) trial with semaglutide showed the geometric means (coefficient of variation in %) of t1/2 was 165 (14.1) h (approximately 1 week). Additionally, the dose dependent increase of the Ctrough values following 4 weeks of treatment with semaglutide 0.25 mg, 0.5 mg and 1.0 mg was 4.4 (31.5), 11.7 (20.2) and 21.2 (19.7) nmol/L, respectively (Kapitza et al., 2015).
![1-s2.0-S0928098717301537-gr1[1].jpg](https://www.excelmale.com/attachments/1-s2-0-s0928098717301537-gr1-1-jpg.27153/ "1-s2.0-S0928098717301537-gr1[1].jpg")
Changes to semaglutide compared with native human GLP-1 are: amino-acid substitutions at position 8 (alanine to alpha-aminoisobutyric acid) and position 34 (lysine to arginine), and acylation of the lysine in position 26 with two ADO moieties followed by a glutamic acid moiety (the ‘spacer’) and a C-18 fatty di-acid side chain (Lau et al., 2015). ADO, 8-amino-3,6-dioxaoctanoic acid.
www.sciencedirect.com
Semaglutide is a human GLP-1 analogue in clinical development for the treatment of T2D. It shares 94% structural homology with native human GLP-1, with three important modifications: amino-acid substitutions at position 8 (alanine to alpha-aminoisobutyric acid) and position 34 (lysine to arginine), and acylation of the lysine in position 26 with a spacer consisting of two 8-amino-3,6-dioxaoctanoic acid (ADO) moieties, a glutamic acid moiety, and a C-18 fatty di-acid side chain (Lau et al., 2015). The fatty di-acid side chain and spacer mediate strong binding with albumin, while the amino-acid substitution at position 34 limits the options for acylation to the one remaining lysine in the sequence; the substitution at position 8 reduces the susceptibility of semaglutide to degradation by DPP-4 (Lau et al., 2015). Together, these modifications prolong the t1/2 of semaglutide; a previous pharmacokinetic (PK) trial with semaglutide showed the geometric means (coefficient of variation in %) of t1/2 was 165 (14.1) h (approximately 1 week). Additionally, the dose dependent increase of the Ctrough values following 4 weeks of treatment with semaglutide 0.25 mg, 0.5 mg and 1.0 mg was 4.4 (31.5), 11.7 (20.2) and 21.2 (19.7) nmol/L, respectively (Kapitza et al., 2015).
Changes to semaglutide compared with native human GLP-1 are: amino-acid substitutions at position 8 (alanine to alpha-aminoisobutyric acid) and position 34 (lysine to arginine), and acylation of the lysine in position 26 with two ADO moieties followed by a glutamic acid moiety (the ‘spacer’) and a C-18 fatty di-acid side chain (Lau et al., 2015). ADO, 8-amino-3,6-dioxaoctanoic acid.
2.1.1. Synthetic procedure for the radioactive building block [3H]-NNC0113-0857
The starting material, NNC0113-3747 (6.6 mg, 6.5 μmol), was dissolved in a solution of N-methyl-2-pyrrolidone (NMP) (1.0 mL) and trifluoroacetic acid (TFA) (5 μL) before 10 wt% Pd/C (6.5 mg) was added. The mixture was subjected to tritium gas (6.9 Ci) and stirred at room temperature. After 4 h, Pd/C was filtered out and the residue co-evaporated (3 × 1.0 mL) with a 1000:1 solution of EtOH/TFA. The residue was dissolved with NMP (1.0 mL) and the radioactive content was determined (180 mCi/mL, 1.6 mL). High-performance liquid chromatography (HPLC) analysis showed that [3H]-NNC0113-0857 had radiochemical purity of 61%.2.1.2. Synthetic procedure for [3H]-semaglutide
The peptide backbone (20.4 mg, 6.0 μmol), was dissolved in H2O (5.0 mL) and the pH adjusted to 11 via the addition of NEt3. The solution of [3H]-NNC0113-0857 in NMP (180 mCi/mL, 1.6 mL) was slowly added over 15 min. After 2 h, the reaction was quenched and neutralised to pH 7 by addition of 1 M CH3COOH (120 μL). The reaction mixture was purified by HPLC (column: Luna® reversed phase C18; A-eluent [0.1 M Tris-HCl, 0.05 M·H3PO4, H2O]/EtOH 8:2, pH 7.4; B-eluent [0.1 M Tris-HCI, 0.05 M·H3PO4, H2O]/EtOH 55:45, pH 7.4) and yielded a [3H]-semaglutide solution of 98% purity. [3H]-semaglutide was desalted on a C18 Sep-Pak® filter and eluted with H2O/EtOH (3:7) into a solution with a radioactive content of 16.7 mCi/mL. The solution was concentrated to dryness on a rotary evaporator and then reconstituted in the following vehicle/API solution of semaglutide (1.34 mg/mL, 1.0 mg/mL or 0 mg/mL), propylene glycol (14 mg/mL), Na2HPO4·2H2O (1.42 mg/mL), phenol (5.5 mg/mL), pH 7.4. HPLC analysis of formulated [3H]-semaglutide gave a radiochemical purity of > 98%.2.1.3. Stability of [3H]-semaglutide
[3H]-semaglutide stability in vehicle was assessed over a 15-day period at 5 °C and 25 °C and confirmed. Radiochemical purity was determined by HPLC. Prestudy stability tests revealed that the tritium tracer showed a satisfactory stability. The amount of tritiated water formed after 15 days’ storage at 25 °C was low (< 0.1%), as was the amount of impurities (~ 2% at 5 °C and ~ 5% at 25 °C).2.1.4. Stability of semaglutide in human material
Stability of the tracer was also assessed in plasma and urine and showed that the [3H]-semaglutide tracer was stable in human blood, plasma and urine for up to at least 4 h at room temperature and up to at least 48 h at nominal + 4, − 20 and − 70 °C. The stability of the [3H]-semaglutide radiotracer was, therefore, considered to be adequate for conducting metabolism studies.
Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species
Semaglutide is a human glucagon-like peptide-1 analogue in clinical development for the treatment of type 2 diabetes. The absorption, metabolism and e…
www.sciencedirect.com
Nelson Vergel
Founder, ExcelMale.com
A pharmaceutical company will seek FDA approval for pediatrics
www.excelmale.com
LUM-201 (ibutamoren, formerly MK-0677) Trials for Pediatric Growth Hormone Deficiency
https://lifescievents.com/event/lumos-pharma-kol-webinar-discussing-interim-results-from-two-phase-2-lum-201-trials-for-pediatric-growth-hormone-deficiency/ Lumos Pharma KOL Webinar Discussing Interim Results from Two Phase 2 LUM-201 Trials for Pediatric Growth Hormone Deficiency
www.excelmale.com
BigTex
Well-Known Member
Why do you say it is a joke?
BigTex
Well-Known Member
Have you ever done hGH? You hit the 4iu+ mark and you have lethargy, carpal tunnel pains and swelling in the fingers. Joints even hurt. Lots of things have side effects, you just have to learn how to handle them. I have taken MK-677 many times over the last 7 years. I always start off with a low dose and work my way up. Eventually the lethargy goes away. I have never gotten the water retention from Mk-677 as I do with hGH and I am oneof the few that does not get hungry.
Yep. Ibutamoren is a crap drug. This is what it feels like, coupled with anxiety.
Its a "selective" ghrelin receptor agonist. Key word, selective. Just like the S in serm.
Maybe for you. Certainly not for the many many people enjoying its benifits right now.
For everyone else, enjoy the GH secretion, increased IGF-1, anti somatostatin benifits. Hell, people are even stacking it with GHRPs to circumvent the somatostatin increase they give etc.
Pro tip: Take the MK before bed so you get none of the hunger sides. Unless of course you want to bulk on it, then take it in the AM.
BigTex
Well-Known Member
Like I said, I am one of those who has used MK-677 with success for many years. I understand the side effects and willing to deal with them. With most drugs, if you are getting unwanted side effects then the dose needs to be lowered. Most are told 25mg is the best dose. Not exactly true, I take 10mgs and get great results. I have always told clients in the past to start off with 12.5mg and adjust up or down based on how you react. Most never listen.
As @bixt just mentioned......take the dose at night. Obviously if you are taking a drug to increase GH levels then you have to understand what increased GH level do in the human body. There is a known interrelationship between GH and sleep. The higher the GH level, the better we sleep. So, there is a linear consistent relationship between slow-wave (SW) sleep and increased GH secretion. Thus, lethargy during the day, especially if you take the dose in the morning. Does it go away, in my experience after about 2-3 weeks it goes away or with a reductionin dose. But again, most don't listend.
I have never seen any research suggesting MK-677 caused anxiety. Is there a chance this side effect happens? I would suggest if you are prone to anxiety, start out with a very low dose and find your sweet spot. If it just doesn't work out, then don't take it. This has to be a very small incidence as it is one of the bestselling SARMS on the market and has been for years.
As @bixt just mentioned......take the dose at night. Obviously if you are taking a drug to increase GH levels then you have to understand what increased GH level do in the human body. There is a known interrelationship between GH and sleep. The higher the GH level, the better we sleep. So, there is a linear consistent relationship between slow-wave (SW) sleep and increased GH secretion. Thus, lethargy during the day, especially if you take the dose in the morning. Does it go away, in my experience after about 2-3 weeks it goes away or with a reductionin dose. But again, most don't listend.
I have never seen any research suggesting MK-677 caused anxiety. Is there a chance this side effect happens? I would suggest if you are prone to anxiety, start out with a very low dose and find your sweet spot. If it just doesn't work out, then don't take it. This has to be a very small incidence as it is one of the bestselling SARMS on the market and has been for years.
Is there any negative feedback mechanisms going on with mk-677? Like is there a downside to using a super low dose of say 2.5-5mg/ day? Like would it shut down endogenous GH secretions, and not leave u with enough GH? Or does it only encourage our brains to make more than what it’s already making, and there’s no negative feedback mechanisms to worry about?
There is no shutdown happening because MK677 just promotes more endogenous GH release.
Taking it before bed can help with some side effects but the half life (24 hours) is too long for this to prevent day time fatigue.
Wrong. The half life for MK is actually low in the order of ~6 hours. It's the IGF-1 boost that may last ~24 hours.
Share this page
Sponsors
Online statistics
- Members online
- 10
- Guests online
- 6
- Total visitors
- 16
