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3 Drug action(c)A + CC(^100) A
80
20
0
10 −^1010 −^910 −^810 −^710 −^610 −^510 −^410 −^3
Concentration (mol/l)
Response (percentage of maximum)
60
40
Figure 3.4.(Cont.)(c)partial agonist acting as competitive inhibitor.Inthis scenario A is a
full agonist; C is a partial agonist. The dotted line, A+C,shows the dose-response curve for A
in the presence of a sub-maximal dose of C. At low concentration of A the combination results
in a greater effect than with A alone but as the dose of A is increased there comes a point at
which the effect of A+Cisless than with A alone. This is because at the crossover point the
only way A can increase the response is by competing for receptors occupied by C. C therefore
appears to act as a competitive inhibitor.
one-fifth of the potency of vecuronium, and therefore is given at five times the dose
for the same effect. The relative flooding of the receptors means that the threshold
receptor occupancy is achieved more rapidly, with a clear clinical benefit.
Non-competitive antagonists
Non-competitive antagonists do not bind to the same site as the agonist, and clas-
sically they do not alter the binding of the agonist. Their antagonism results from
preventing receptor activation through conformational distortion. Their action can-
not be overcome by increasing the concentration of an agonist present. An example is
the non-competitive antagonism of ketamine with glutamate at NMDA receptors in
the CNS. Recent classification of antagonists now groups non-competitive inhibitors
and negative allosteric modulators (see later) together. This is because most non-
competitive inhibitors, when investigated carefully, do alter agonist binding.
Allosteric modulation of receptor binding
Notall drugs with reversible activity will produce effects that fit neatly into either
the competitive or non-competitive category. Some drugs can bind to sites distant
from the agonist receptor site, yet still alter the binding characteristics of the agonist.