Abstract: The present invention relates to methods for determining the efficiency of an ion channel ligand comprising (a) contacting a cell expressing the ion channel with (i) plasma of an animal and (ii) the ion channel ligand and (b) determining the effect of the ion channel ligand on the cell.

Abstract: The present invention relates to methods for determining the in vivo efficiency of a sodium-proton-exchanger (NHE) ion channel ligand comprising the steps of: (a) contacting a cell expressing a sodium-proton-exchanger (NHE) ion channel in vitro with either (i) plasma of an animal and the ion channel ligand or (ii)) the plasma of an animal which has been administered the ion channel ligand; (b) determining the effect of the ion channel ligand on the cell; c) determining ion channel ligand availability by comparing the ligand concentration in the plasma to the concentration of ligand administered; and d) correlating the effect of the ion channel ligand on the cell with the ligand availability to determine the in vivo efficiency of the ligand.

Abstract: The present invention relates to methods for determining the efficiency of an ion channel ligand comprising (a) contacting a cell expressing the ion channel with (i) plasma of an animal and (ii) the ion channel ligand and (b) determining the effect of the ion channel ligand on the cell.

Abstract: Transporters are an emerging target family with enormous potential, offering scientific and economic opportunities The sodium/calcium exchanger is an important mechanism for removing Ca2+ from diverse cells. In heart, it extrudes Ca2+ that has entered through Ca2+ channels to initiate contraction, while Na+ enters the heart cell. It is of considerable interest to identify compounds that modulate, not only the calcium export activity (forward mode), but also the calcium import activity (reverse mode) of sodium/calcium exchangers. The present invention is directed to a fluorescence-based assay for detecting NCX “reverse mode” modulating compounds. It further refers to a kit of parts comprising cells expriming NCX and the use of the kit of parts to test a compound for activity as an agonist or antagonist of NCX.

Abstract: Transporters are an emerging target family with enormous potential, offering scientific and economic opportunities. The sodium/calcium exchanger is an important mechanism for removing Ca2+ from diverse cells. In heart, it extrudes Ca2+ that has entered through Ca2+ Channels to initiate contraction, while Na+ enters the heart cell. It is of considerable interest to identify Compounds that modulate the activity of sodium/calcium exchangers. The present invention is directed to a fluorescence-based assay for detecting NCX and NCKX “forward mode” modulating Compounds. It further refers to a kit of parts comprising cells expriming a sodium/calcium exchanger and the use of the kit of parts to test a Compound for activity as an agonist or antagonist of a sodium/calcium exchanger.

Abstract: The invention relates to substituted 4-phenyltetrahydroisoquinolines of formula I wherein R1-R8, N, W, X and Z are defined herein. These compounds and pharmaceutical compositions comprising them are useful in the treatment of respiratory disorders, sleep apnea, kidney disorders, high blood pressure, hypertension, disorders of the central nervous system and the like.

Abstract: The present invention relates to substituted 4-phenyltetrahydroisoquinoline compounds of the structure of formula I and pharmaceutical compositions comprising them wherein the R groups are herein defined. These are excellent inhibitors of the sodium-hydrogen exchanger (NHE), in particular of the sodium-hydrogen exchanger of subtype 3 (NHE3). As such these compounds are useful in the treatment of various disorders of the renal and respiratory systems such as acute or chronic renal failure, pulmonary complications, biliary function disorders, respiratory disorders such as snoring or sleep apneas and cardiovascular/central nervous system disorders such as stroke.

Abstract: Transporters are an emerging target family with enormous potential, offering scientific and economic opportunities. The Sodium/Calcium exchanger is an important mechanism for removing Ca2+ from diverse cells. In heart, it extrudes Ca2+ that has entered through Ca2+ channels to initiate contraction, while Na+ enters the heart cell. It is of considerable interest to identify compounds that modulate the activity of Sodium/Calcium exchangers. The present invention is directed to a fluorescence-based assay for detecting NCX “forward mode” modulating compounds. It further refers to a kit of parts comprising cells expriming NCX and the use of the kit of parts to test a compound for activity as an agonist or antagonist of NCX.

Abstract: The invention relates to substituted 4-phenyltetrahydroisoquinolines of formula I wherein R1-R8, N, W, X and Z are defined herein. These compounds and pharmaceutical compositions comprising them are useful in the treatment of respiratory disorders, sleep apnea, kidney disorders, high blood pressure, hypertension, disorders of the central nervous system and the like.

Abstract: The present invention relates to substituted 4-phenyltetrahydroisoquinoline compounds of the structure of formula I and pharmaceutical compositions comprising them wherein the R groups are herein defined. These are excellent inhibitors of the sodium-hydrogen exchanger (NHE), in particular of the sodium-hydrogen exchanger of subtype 3 (NHE3). As such these compounds are useful in the treatment of various disorders of the renal and respiratory systems such as acute or chronic renal failure, pulmonary complications, biliary function disorders, respiratory disorders such as snoring or sleep apneas and cardiovascular/central nervous system disorders such as stroke.

Abstract: Substituted thienoimidazoles with a backbone structure of formula I or II: These substituted thienoimidazoles are useful in prevention or treatment of various disorders, including respiratory disorders.

Abstract: Substituted thienoimidazoles with a backbone structure of formula I or II: These substituted thienoimidazoles are useful in prevention or treatment of various disorders, including respiratory disorders.