Allosteric regulation of binding and function at GPCRS

Allosteric ligands, in contrast to competitive agonists and antagonists, act to tune up (or down) receptor function whilst maintaining the important temporal aspects of intercellular receptor signalling in the nervous system. In addition, some allosteric ligands exhibit 'absolute subtype selectivity'; action at one subtype but no action at any concentration at other subtypes. Some allosteric ligands also have pharmacological actions in the absence of orthosteric ligands and can act as inverse agonists or agonists in their own right by modulating constitutive activity. Examples of the novel pharmacological aspects and mechanisms of the actions of a number of allosteric ligands on muscarinic and adenosine A(1) receptors are described.