ABSTRACT
G-protein-coupled receptors represent the single largest family of cell surface receptors involved in signal transduction. It is estimated that several hundred distinct members of this receptor family in humans direct responses to a wide variety of chemical transmitters, including biogenic amines, amino acids, peptides, lipids, nucleosides, and large polypeptides. They therefore represent major targets for the development of new drug candidates with potential application in all clinical fields. Many currently used therapeutics act by either activating (agonists) or blocking (antagonists) these receptors; widely used examples are 13-adrenoceptor agonists for asthma and antagonists for hypertension, histamine Hr and Hrreceptor antagonists for allergies and duodenal ulcers, respectively, opioid receptor agonists (e.g., morphine) as analgesics, dopamine receptor antagonists as antipsychotics, and 5HT receptor agonists (e.g., sumitriptan) for migraine. The concept of efficacy is a fundamental parameter in the analysis of drug action on receptors, and the ranking of drugs based on the amplitude of the response they induce can be a determining factor in their therapeutic utility. Classical receptor theory describes receptors (R) as quiescent until activated by the binding of an agonist (A), with the resulting binary complex (AR) having affinity for its cognate G-protein (1-3). Thus, the concept of ligand efficacy
