P1: PCX Printer: Yet To Come
9780521704632c03 CUFX213A/Peck 9780521618168 December 27, 2007 13:30
3 Drug action(c)A100806040200
10 −^1010 −^910 −^810 −^710 −^610 −^510 −^410 −^3
Concentration (mol/l)Response (percentage of maximum)BCFigure 3.3.(Cont.)Receptor antagonism
Antagonists exhibit affinity but no intrinsic activity. Their binding may be either
reversible or irreversible.Reversible
Reversible antagonists may either be competitive or non-competitive.Competitive antagonists
For competitive antagonists the effect of the antagonist may be overcome by increas-
ing the concentration of the agonist – the two molecules are competing for the same
receptor and the relative amounts of each (combined with receptor affinity) deter-
mine the ratios of receptor occupation. In the presence of a competitive inhibitor
the log[dose] versus response curve is shifted to the right along the x-axis; the extent
of this shift is known as the dose-ratio (Figure3.4(a)). It defines the factor by which
agonist concentration must be increased in order to produce equivalent responses
in the presence and absence of a competitive inhibitor. The pA 2 value, the negative
logarithm of the concentration of antagonist required to produce a dose-ratio of 2, is
used to compare the efficiency of competitive antagonism for different antagonists
at a given receptor.
Examples of competitive inhibition include the non-depolarizing muscle relaxants
competing with acetylcholine for cholinergic binding sites at the nicotinic receptor
of the neuromuscular junction andβ-blockers competing with noradrenaline at
β-adrenergic receptor sites in the heart.