Pharmacodynamics (PD) is how a compound produces its effect once it reaches the target.
- Agonist — a ligand that activates a receptor (semaglutide agonizes GLP-1; testosterone agonizes the androgen receptor).
- Antagonist — a ligand that blocks a receptor without activating it (caffeine antagonizes adenosine; yohimbine antagonizes alpha-2). Antagonists work by preventing the natural signal.
- Partial agonist / inverse agonist — partial = weaker-than-full activation; inverse = pushes the receptor below baseline.
- Affinity — how tightly a compound grips its target. Efficacy — how big an effect it produces once bound. A drug can bind tightly but do little (high affinity, low efficacy). SARMs are the whole point of this distinction: they bind the androgen receptor with tissue-selective efficacy (strong in muscle, weak in prostate).
- Selectivity — how many different targets it hits. Ipamorelin is selective (only the ghrelin receptor); older GHRPs also hit cortisol/prolactin receptors — that's why ipamorelin has fewer side effects.
- Dose-response — more dose = more effect, up to a ceiling (or a toxicity cliff, as with DNP where the effective and lethal doses nearly overlap — the therapeutic index, the safety gap between "works" and "harms").
- Allosteric modulation — binding a site other than the main one to tune the receptor up or down (L-theanine and the racetams do this).
- Tolerance / downregulation — with constant stimulation, the cell removes receptors, so you need more for the same effect (caffeine, nicotine, phenibut). This is why cycling matters.
✅ Key takeaways
- An agonist activates a receptor; an antagonist blocks it; partial/inverse agonists activate weakly or below baseline.
- Affinity (how tightly it binds) ≠ efficacy (how big an effect) — SARMs bind the androgen receptor with tissue-selective efficacy.
- Dose-response has a ceiling, and sometimes a toxicity cliff; the therapeutic index is the safety gap between effective and toxic dose (razor-thin for DNP).
- Constant stimulation causes tolerance (receptor downregulation) — which is why stimulants need cycling.
🧠 Check yourself
Q1 What's the difference between an agonist and an antagonist?
An agonist activates a receptor (mimics the natural signal, e.g. semaglutide on GLP-1); an antagonist occupies it without activating, blocking the natural signal (e.g. caffeine on adenosine).
Q2 A drug binds its target very tightly but produces little effect. Which is high, which is low — affinity or efficacy?
High affinity (tight binding), low efficacy (small effect). They're independent — the whole point of SARMs.
Q3 Why do stimulants stop working as well over time?
Tolerance: constant stimulation makes the cell remove receptors (downregulation), so you need more for the same effect. Hence cycling.