ABSTRACT
G-protein-coupled receptors (GPCRs) constitute a very important class of drug targets. It is estimated that approximately half of the marketed medicines exert their action through members of this protein class (1). These membrane-bound macromolecules most probably share the architecture of the visual pigment rhodopsin, i.e., a cavity with seven transmembrane a-helical domains as outer boundaries, ideally suited to accommodate small molecules or molecular fragments. Such molecules are the endogenous agonists in the first place, i.e., hormones and neurotransmitters. They act as ‘‘primary messengers’’ to convey signals into the cell that give rise to, among others, the production of ‘‘second messengers’’ such as cyclic adenosine monophosphate (cAMP), leading to a cellular response. Synthetic agonists, antagonists, and inverse agonists have been introduced to the market, yielding the rich repertoire of current medicines.
