This volume reflects the current state of thinking and debates with regard to inverse agonism. It constitutes the first book published on this issue and holds the contributions and recorded discussions of the 10th Esteve Foundation Symposium held in 2002.
Inverse agonism at G-protein-coupled receptors is a novel pharmacological concept with important consequences for the understanding of receptor mechanisms and drug action. Since its first description in 1989 the concept of inverse agonism has dramatically changed the view on current and future medicines. Next to traditional agonists and antagonists the drug repertoire has been expanded now with a novel category of ligands, i.e. 'inverse agonists'.
About the Esteve Foundation. Introduction. Different mechanisms of
negative efficacy. Distinguishing inverse agonists from negative antagonists
(T. Costa et al.). Novel approaches to enhance the detection of receptor
constitutive activity and inverse agonists (G. Milligan). From inverse
agonism to "Paradoxical Pharmacology" (R.A. Bond, K.L.J. Evans, Z.
Callaerts-Vegh). Different inverse agonist activities of beta-adrenergic
receptor antagonists - pharmacological characterization and therapeutical
implications in the treatment of chronic heart failure (C. Maack, M. Bohm
(Germany). Inverse agonism at beta1 -adrenergic receptors (M.J. Lohse, C.
Hoffmann, S. Engelhardt). Physiological and pathological role of the
constitutively active alpha1D-adrenoceptors (P. D'Ocon). Inverse agonism at
cannabinoid receptors (R.G. Pertwee). Inverse agonism at adenosine A1
receptors (R.A.F. de Ligt, A. Lorenzen, A.P. IJzerman). Differential ligand
efficacy at h5 HT1A receptor-coupled G-protein subtypes: a commentary (A.
Newman-Tancredi). 5-HT2c constitutive receptor activity: effector
pathway-dependence (K.A. Berg, W.P. Clarke). Modulation of constitutive GPCR
activity: a way of life? (R. Leurs et al.). Constitutive activity of the
recombinant and native histamine H3 receptor (J.M. Arrang et al.). Inverse
agonism of the antipsychotic drugs at the D2 dopamine receptor (P.G.
Strange). Inverse agonism at dopamine D2 receptors: a receptor recalcitrant
to high levels of constitutive activation (T. Wurch, E.A. Boutet-Robinet,
P.J. Pauwels). Platelet-activating factor receptor: differential regulation
and signaling by agonists and inverse agonists (D.J. Dupre, M
Rola-Pleszczynski, J. Stankova). AgRP, physiological role of an inverse
agonist (R.A.H. Adan, W.A.J. Nijenhuis, M.J.H. Kas). Inverse agonism at
neurotensin receptors NTS1 and NTS2 (P. Kitabgi). The thyrotropin receptor, a
GPCR with a built in inverse agonist (G. Vassart). Inverse agonism and the
PTH/PTHrP receptor (R. Gensure, P.H. Carter, T.J. Gardella). Inverse agonists
to explore the mechanisms of metabotropic glutamate receptor activity (L.
Prezeau et al.). Control of constitutive activity of metabotropic glutamate
receptors by Homer proteins (L. Fagni et al.). General discussion. Author
index.
