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ForumsOther Peptides & Research CompoundsSelank and Semax — May 2025

Selank and Semax — May 2025

SandraNC_45 Tue, Nov 11, 2025 at 8:25 AM 27 replies 1,290 viewsPage 1 of 6
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SandraNC_45
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Nov 11, 2025 at 8:25 AM#1

Posting this because the summary going around does not say what the paper says, and the difference matters for how people here are using it.

The mechanism is more central than most summaries suggest. Receptor agonism in the arcuate nucleus activates POMC neurons and inhibits AgRP/NPY signalling, and the downstream MC4R pathway is the same one disrupted in monogenic obesity — convergent genetic evidence that the target is the right one. Peripherally there is glucose-dependent insulin secretion, glucagon suppression and delayed gastric emptying, but the gastric component largely adapts over months while the central effect persists, which is why the durable effect is appetite rather than fullness.

Where I think it is weakest: the subgroup findings are the part I trust least — with enough subgroups something is always significant, and these were not all pre-registered.

What would genuinely help is knowing which effects tachyphylax and which persist, because the answer explains why tolerability improves while the appetite effect keeps working. Tell me what I have not thought of.

Note on sourcing:
Figures above are from the primary publication rather than the press summary. If a number here disagrees with one you have, post yours and we will work out which of us is reading a secondary source.
38 8FranDenver, Dr.BariatricHTX, LindaRN_retired and 35 others
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DanielChem_CHI
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Mar 2024
Chicago, IL
Nov 11, 2025 at 8:45 AM#2
SandraNC_45 said:
The mechanism is more central than most summaries suggest.

Amycretin (AMY/GLP-1 dual agonist) emerging data relevant to the pharmacology: Phase 1 showed -13.1% body weight at only 12 weeks, the fastest trajectory ever seen for an anti-obesity agent[1].

Amylin receptor agonism enhances satiety signaling through the area postrema and reduces glucagon secretion. Combined with GLP-1R agonism, this dual mechanism may produce even greater efficacy than current agents.

Early-stage data — interpret with caution. But the trajectory is extraordinary.

References:
[1] Novo Nordisk investor presentation, September 2023.
37 7Dr.DermMIA, fiona_VT, denise_HTX and 34 others
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LipidDoc_ATL
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Atlanta, GA
Nov 11, 2025 at 9:05 AM#3
SandraNC_45 said:
The mechanism is more central than most summaries suggest.

This is where I part company with the consensus forming above. The pharmacokinetics explain nearly every practical question asked here. Albumin binding above 99% slows clearance enough to make weekly dosing possible; a terminal half-life near a week means four to five weeks to steady state and therefore a four-week titration interval; subcutaneous bioavailability around 89% means injection site barely matters. Those three facts answer most timing questions before they are asked.

Last edited: Nov 11, 2025 at 2:05 PM
36 6AttorneyGrant, DebRD_ATL, KristenIndy and 33 others
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traveltech_sara
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Nov 11, 2025 at 9:25 AM#4
LipidDoc_ATL said:
The pharmacokinetics explain nearly every practical question asked here.

Semaglutide structural biology relevant to the pharmacology: semaglutide is a 31-amino acid peptide with 94% homology to native GLP-1(7-36). Three key modifications enable its pharmacokinetic profile:

  1. Aib8 substitution: DPP-4 resistance (prevents enzymatic degradation)
  2. Arg34 substitution: improved chemical stability
  3. C18 fatty diacid at Lys26: albumin binding → long half-life

These three modifications transform a peptide with a 2-minute half-life (native GLP-1) into one with a 168-hour half-life (semaglutide). A masterclass in peptide engineering.

Last edited: Nov 11, 2025 at 12:25 PM
35 5NurseAsh_DET, BenResearch_OR, MikeKY_noInsulin and 32 others
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tammy_FL
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Nov 11, 2025 at 11:15 AM#5
DanielChem_CHI said:
Amycretin (AMY/GLP-1 dual agonist) emerging data relevant to the pharmacology: Phase 1 showed -13.1% body weight at only 12 weeks, the fastest…

Adding a me-too, because a thread of one person's experience is not much use.

34 4mike_mealprep, NicoleRaleigh, james_edin and 31 others
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