Maximal Effect (Emax)

Emax is the upper asymptote of the sigmoid, and it belongs jointly to the ligand and the system rather than to the ligand alone. A full agonist reaches whatever maximum the tissue is capable of; a partial agonist plateaus below it even at complete receptor occupancy, because its intrinsic efficacy is lower. Where receptor reserve is large, a full agonist can hit its maximum while occupying only a fraction of the available receptors, which is why the plateau often arrives at concentrations far under the binding constant.

Ceilings are visible in clinical data as flattening at the top of a dose range. In obesity and diabetes trials of incretin agonists, the increment in weight or glycated haemoglobin reduction between the two highest doses is consistently smaller than the increment between the lowest and the middle, while gastrointestinal adverse events continue to climb across the whole range. That divergence, and not the efficacy curve alone, is what caps the licensed dose.

The practical consequence is that potency and maximum answer different questions. If the therapeutic goal needs the full physiological response, a less potent full agonist beats a more potent partial one, and no amount of dose escalation closes the gap. Once the plateau is reached, additional exposure adds only whatever the safety curve is doing at that point.

Two presentation habits obscure this. Normalising every curve so its own top is 100 per cent hides partial agonism entirely, since a compound producing a third of the reference response looks identical to a full agonist once rescaled. The other confusion is between pharmacological maximum and maximum tolerated dose: a trial that stops escalating because of nausea has found a tolerability limit, not a ceiling on effect, and the two should not be quoted interchangeably.