Publications

Drug-receptor interactions were earlier quanti?ed in terms of af?nity and ef?cacy only but residence time has now also been recognized to affect clinical performance. Different approaches to measure drug binding kinetics are brie?y presented and critically evaluated with the help of simulations. Based on the antagonist's ability to reduce agonist-evoked responses, two main methods are used in functional assays. Radiolabelled drug binding to cell ...

UNLABELLED: Abnormal glutamate transmission is involved in various neurologic disorders, such as epilepsy, schizophrenia, and Parkinson disease. At present, no imaging techniques are capable of measuring acute fluctuations in endogenous glutamate levels in vivo. We evaluated the potential of (11)C-ABP688, a PET ligand that binds to an allosteric site of the metabotropic glutamate 5 receptor, in rats by using small-animal PET and β-microprobes ...

Background and purpose: Insulin-regulated aminopeptidase ( IRAP) and the insulin-dependent glucose transporter GLUT4 colocalize in specific intracellular vesicles (that is, GLUT4 vesicles). These vesicles move slowly to the cell surface, but their translocation is markedly enhanced by insulin, resulting in higher glucose uptake. Previous studies of the insulin-mediated translocation of IRAP to the cell surface have been hampered by the laborious ...

Introduction
In many situations, optimal drug therapy requires continuing, high levels of target occupancy and this notion has led pharmacologists to focus attention to the rate by which drug candidates dissociate from their target. To this end, radioligand dissociation experiments are often carried out on in vitro models such intact cells and membranes thereof but the interpretation of the collected data is sometimes ambiguous.
Areas ...

Excitatory amino acid transporters (EAATs) are important regulators of amino acid transport and in particular glutamate. Recently, more interest has arisen in these transporters in the context of neurodegenerative diseases. This calls for ways to modulate these targets to drive glutamate transport, EAAT2 and EAAT3 in particular. Several inhibitors (competitive and noncompetitive) exist to block glutamate transport; however, activators remain ...

UNLABELLED: Phosphodiesterases are enzymes that inactivate the intracellular second messengers 3',5'-cyclic adenosine-monophosphate and/or cyclic guanosine-monophosphate. Of all 11 known phosphodiesterase families, phosphodiesterase-10A (PDE10A) has the most restricted distribution, with high expression in the striatum. PDE10A inhibitors are pursued as drugs for treatment of neuropsychiatric disorders. We have synthesized and evaluated ...