BPS2012 Help Us Help You (Topic 5- Bias and Allosteric Modulator) by Ong Yong Sze

In some systems, a partial agonist can produce the same maximum response as a full agonist. Should we still call it a partial agonist?

ongyongsze — 2025-08-28 06:52:35 UTC

Yes, because “partial” describes the intrinsic efficacy of the drug–receptor complex, not the system’s output.

In a system with spare receptors, the drug’s lower efficacy is compensated for, but the drug itself hasn’t changed.

Silent Allosteric Modulator

ongyongsze — 2025-08-28 06:55:32 UTC

If a SAM doesn’t change activity, why might it still matter pharmacologically?

It can block other allosteric ligands (like “silent competition”) or stabilize a receptor conformation that affects long-term regulation.

What’s the difference between a PAM and an allosteric agonist if both enhance activity?

ongyongsze — 2025-08-28 06:56:00 UTC

A PAM needs the orthosteric agonist to work (it boosts affinity/efficacy). An allosteric agonist can activate the receptor by itself at the allosteric site.

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ongyongsze — 2025-08-28 07:02:36 UTC

The "K" in Black & Leff's model:

ongyongsze — 2025-08-28 07:07:23 UTC

K (or KA) = the concentration of agonist required to occupy half of the available receptors.

K (or KA) = Koff /Kon

Low K (less dissociation)→ high affinity (tight binding, less agonist needed).
High K (more dissociation)→ low affinity (weak binding, more agonist needed).