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its own in the absence of the agonist or antagonist. Allosteric enhancers are a

subgroup of these allosteric modulators;

• Ago-allosteric modulator: This is a ligand that can act as both an allosteric agonist and
  as an allosteric modulator altering the efficacy and/or the potency of agonists acting
  on the orthosteric site.

The presence of allosteric sites is important in drug discovery since in principle drugs

acting at this site may modify the physiological response transduced by the receptor

(Section 18.2.2).

17.2.4 Quantitative characterisation of receptor–ligand binding

The previous discussion has shown that ligands capable of binding to a receptor may

be of a variety of types. To fully characterise any ligand it is essential that its binding

be expressed in quantitative terms. This is achieved by binding studies. If under the

conditions of the binding studies the total concentration of ligand is very much

greater than that of receptor (so-calledsaturation conditions), changes in ligand

concentration due to receptor binding can be ignored but changes in the free

(unbound) receptor concentration cannot. Hence if:

[Rt] is the total concentration of receptor that determines the maximum binding

capacity for the ligand

[L] is the free ligand concentration

[RL] is the concentration of receptor–ligand complex

then [RtRL] is the concentration of free receptor.

At equilibrium, the forward and reverse reactions for ligand binding and

dissociation will be equal:

kþ 1 ð½RtŠ½RLŠÞ½LŠ¼k 1 ½RLŠ

Orthosteric

site

1

2

3 Plasma membrane

Allosteric

site

Effector-coupling

site(s)

Fig. 17.3Types of allosteric modulator. Allosteric ligands can affect receptor function in three general ways.

(1) Allosteric modulation of orthosteric ligand-binding affinity; (2) allosteric modulation of orthosteric ligand

efficacy; (3) direct allosteric agonism. (Reproduced from Langmead, C. J. and Christopoulos, A. (2006). Allosteric

agonists of 7TM receptors: expanding the pharmacological toolbox.Trends in Pharmacological Sciences, 27 ,

475–481, by permission of Elsevier Science.)

671 17.2 Quantitative aspects of receptor–ligand binding