DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

Competitive
A Ι
Pseudo-Irreversible
A
Ι
Allosteric
A Ι
P
% Maximal Effect
% Maximal Effect
% Maximal Effect
% Maximal Effect
100
50
0
100
50
0
100
50
0
100
50
A
B
Competitive antagonism
Noncompetitive
antagonism
C
D
Control
Antagonism
Potentiation
L
Ι
Log [A]
Log [A]
3
Ι
10 Ι
L L L
Log [A]
47
CHAPTER 3
PHARMACODYNAMICS: MOLECULAR MECHANISMS OF DRUG ACTION
0
Log [A]
Figure 3–4. Mechanisms of receptor antagonism. A. Competitive antagonism occurs when the agonist A and antagonist I compete for
the same binding site on the receptor. Response curves for the agonist are shifted to the right in a concentration-related manner by the
antagonist such that the EC 50
for the agonist increases (e.g., L versus L′, L′′, and L′′′) with the concentration of the antagonist. B. If
the antagonist binds to the same site as the agonist but does so irreversibly or pseudo-irreversibly (slow dissociation but no covalent
bond), it causes a shift of the dose-response curve to the right, with further depression of the maximal response. Allosteric effects occur
when an allosteric ligand I or P binds to a different site on the receptor to either inhibit (I) the response (see panel C) or potentiate (P)
the response (see panel D). This effect is saturable; inhibition or potentiation reaches a limiting value when the allosteric site is fully
occupied.