Ion Channels in Drug Discovery - focus on biological assays

摘要: ABSTRACT Ion channels are well characterised drug targets. However, the techniques used to study ion channel pharmacology have not been particularly applicable modern discovery. The aim of this thesis was examine usefulness both established and novel methods in discovery pharmacological characterisation drugs interacting with channels. Three different classes studied; GABA A receptor representing classical ligand-gated channel, voltage-gated sodium (Na V -1.7) newly discovered non-selective cation Transient Receptor Potential Melastatin-8 (TRPM8). Due difficulty expression purification membrane proteins, no crystal structures receptors currently available structure-based design is directly applicable. Using pharmacophore modelling site-directed mutagenesis, ligand interactions were studied at a structural level. model for benzodiazepine binding site (BzR) on