title: Supra-physiological efficacy at GPCRs: superstition or super agonists?
abstract: The concept of 'super agonism' has been described since the discovery of peptide hormone analogues that yielded greater functional responses than the endogenous agonists, in the early 1980s. It has remained an area of debate as to whether such compounds can really display greater efficacy than an endogenous agonist. However, recent pharmacological data, combined with crystal structures of different GPCR conformations and improved analytical methods for quantifying drug action, are starting to shed light on this phenomenon and indicate that super agonists may be more than superstition.
authors: Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
authors: Christopher J
authors: CJ
authors: Langmead
authors: Arthur
authors: A
authors: Christopoulos
mesh_terms: D000818:Animals; D005347:Fibroblasts / Q000187:drug effects*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D043585:Receptor, Muscarinic M2 / Q000819:agonists*
chemical_list: D007555:Isoxazoles; D018721:Muscarinic Agonists; D000644:Quaternary Ammonium Compounds; D043585:Receptor, Muscarinic M2; C000591650:iperoxo; D019204:GTP-Binding Proteins