Current Neuropharmacology - Volume 5, Issue 3, 2007

Drugs acting at G-protein coupled receptors (GPCRs) represent the core of modern medicine. Traditionally, these drugs target the orthosteric site of the receptors, i.e. the binding site of the endogenous agonist. An increasing number of patents describe synthetic allosteric modulators of GPCRs, which influence receptor activity at sites distinct from the orthosteric site. This documents that the search for allosteric modulators of G Read More

The description of the allosteric modification of receptors to affect changes in their function requires a model that considers the effects of the modulator on both agonist affinity and efficacy. A model is presented which describes changes in affinity in terms of the constant α (ratio of affinity in the presence vs the absence of modulator) and also the constant ξ (ratio of intrinsic efficacy of the agonist in the presence vs absenc Read More

Muscarinic acetylcholine receptors (mAChRs) are prototypical Family A G protein coupled-receptors. The five mAChR subtypes are widespread throughout the periphery and the central nervous system and, accordingly, are widely involved in a variety of both physiological and pathophysiological processes. There currently remains an unmet need for better therapeutic agents that can selectively target a given Read More

Class B GPCR's are activated by peptide ligands, typically 30-40 amino acid residues, that are involved in major physiological functions such as glucose homeostasis (glucagon and glucagon-like peptide 1), calcium homeostasis and bone turnover (parathyroid hormone and calcitonin), and control of the stress axis (corticotropin-releasing factor). Peptide therapeutics have been developed targeting these receptors but devel Read More

The calcium (Ca2+)-sensing receptor (CaR) belongs to family C of the G-protein coupled receptors (GPCRs). The receptor is activated by physiological levels of Ca2+ (and Mg2+) and positively modulated by a range of proteinogenic L-α-amino acids. Recently, several synthetic allosteric modulators of the receptor have been developed, which either act as positive modulators (termed calcimimetics) or negative Read More

The metabotropic glutamate receptor family comprises eight subtypes (mGlu1-8) of G-protein coupled receptors. mGlu receptors have a large extracellular domain which acts as recognition domain for the natural agonist glutamate. In contrast to the ionotropic glutamate receptors which mediate the fast excitatory neurotransmission, mGlu receptors have been shown to play a more modulatory role and have been propos Read More

γ-aminobutyric acid (GABA) plays important roles in the central nervous system, acting as a neurotransmitter on both ionotropic ligand-gated Cl--channels, and metabotropic G-protein coupled receptors (GPCRs). These two types of receptors called GABAA (and C) and GABAB are the targets of major therapeutic drugs such as the anxiolytic benzodiazepines, and antispastic drug baclofen (lioresal®), respectively. Although the mu Read More

Addiction involves complex physiological processes, and is characterised not only by broad phenotypic and behavioural traits, but also by ongoing molecular and cellular adaptations. In recent years, increasingly effective and novel techniques have been developed to unravel the molecular implications of addiction. Increasing evidence has supported a contribution of the nuclear transcription factor CREB in the development Read More

Prenatal exposure to tobacco smoke is a major risk factor for the newborn, increasing morbidity and even mortality in the neonatal period but also beyond. As nicotine addiction is the factor preventing many women from smoking cessation during pregnancy, nicotine replacement therapy (NRT) has been suggested as a better alternative for the fetus. However, the safety of NRT has not been well documented, and animal studies Read More

Due to an overlook on the author's side, some of the references in the legends of figures of an article L-Glutamate and its ionotropic receptor in the nervous system of cephalopods” by A. Di Cosmo, C. Di Cristo and J. B. Messenger, published in the journal Current Neuropharmacology Volume 4, issue 4, October 2006, were wrong. The complete list of correct references is as follows: Figure 1 Reference 49 Figure 2 Reference 16 Fi Read More