PHARM/PCS V5 · Procedure 12 Receptor Pharmacology
Dissociation Constant I: Agonists (Furchgott Method)
Estimate a full agonist's dissociation constant KA from dose-response curves measured before and after partial irreversible receptor blockade.
What it computes
Determines the dissociation constant KA of an agonist using the method of partial irreversible blockade. Equieffective concentration pairs (A′, A) are obtained from dose-response curves before and after irreversible antagonist treatment. A double-reciprocal plot of 1/A vs. 1/A′ yields a regression line whose slope and intercept give KA.
Inputs and outputs
You provide
- Equieffective concentration pairs: A′ after blockade and A before blockade, one pair per line
PHARM/PCS reports
- The fitted double-reciprocal line, slope and intercept
- KA, the agonist dissociation constant
- The double-reciprocal plot with the fitted line
When to use it
When you need a full agonist's affinity for its receptor and can partially, irreversibly inactivate receptors (for example, with a site-directed alkylating agent) to shift the curve. It's the first of three KA methods here: partial agonists use Procedure 13, relaxation kinetics use Procedure 14.
Reading the results
The method rests on equieffective concentrations reflecting equal receptor occupancy before and after blockade, so clean, well-matched dose-response curves matter more than sheer point count. A slope or intercept near zero sends KA to infinity or negative, a sign the blockade was too light or too heavy to separate the curves usefully.
Judge the fit first
Double-reciprocal plots magnify error in small values. This procedure applies the method exactly as the book describes and does not weight the data, so look at the line before you quote KA.
This page describes the procedure. Calculations run inside the licensed PHARM/PCS V5 application. PHARM/PCS is a trademark of MCS Scientific LLC.