Published in Current opinion in pharmacology
Glutamate is probably the most important excitatory transmitter in the vertebrate central nervous system. Its multiple functional roles in the brain and spinal cord make therapeutic manipulation of these systems fraught with difficulties. There has, however, been recent progress in pharmacological manipulations of NMDA receptor subtypes and non-NMD...
Published in Current opinion in pharmacology
Major recent findings in peripheral opioid analgesia include the relative lack of tolerance under inflammatory conditions, tetrapeptides as novel peripherally restricted compounds, the potent anti-inflammatory activity of mu and kappa agonists and the identification of selectins as important molecules governing the homing of opioid cells to injured...
Published in Current opinion in pharmacology
The majority of genes encoding G protein-coupled receptors were isolated by methods based on sequence similarities found throughout this family. Experimental techniques have exploited these similarities (including low-stringency hybridization, polymerase chain reaction and electronic database searching) to identify genes encoding many pharmacologic...
Published in Current opinion in pharmacology
The GABA(A) receptor is a pluripotent drug target mediating anxiolytic, sedative, anticonvulsant, muscle relaxant and amnesic activity. These drug actions have now been attributed to defined receptor subtypes. Thus, precise guidelines are available for the development of novel drugs with more selective action and less side effects than those curren...
Published in Current opinion in pharmacology
Increased knowledge of the molecular diversity of sodium channel alpha- and beta-subunits, and their distribution of expression have been highlights of the past year. The development of subtype-specific channel blockers remains elusive, but the discovery of selective inhibitors such as mu-conotoxins promises useful antagonists in the near future.
Published in Current opinion in pharmacology
Published in Current opinion in pharmacology
Over the last year the combinations of G-protein-coupled receptors that are known to form heterodimeric complexes has rapidly increased. For example, dopamine receptors can dimerize with both somatostatin and adenosine receptors. These studies have been aided by improved technologies to monitor protein/protein interactions in living cells. Crosstal...
Published in Current opinion in pharmacology
Major progress in our understanding of the mechanisms of anaesthesia has been made during the past year. Several key advances in defining very specific sites of action on ligand-gated ion channels have been described. Furthermore, new techniques have become available for addressing the identification of binding sites and transduction mechanisms on ...
Published in Current opinion in pharmacology
Glutamate receptors (GluRs) are localized in the periphery on nociceptive primary afferent terminals. Studies in animal models of pain demonstrate that peripheral glutamate is involved in nociceptive transmission in the normal and the inflamed state and that modulation of peripheral GluRs reduces pain behaviors and nociceptor activity. These data p...
Published in Current opinion in pharmacology
Recent cloning efforts have identified families of ion channels that may be involved in signaling noxious proton accumulation in tissue. Some conduct potassium ions outward and are closed by excess protons, others are opened under this condition carrying cations inward and their putative function is in their name ('acid sensing'), and again another...
