Sahdeo S.,Roche Holding AG |
Sahdeo S.,University of California at Davis |
Wallace T.,Roche Holding AG |
Wallace T.,SRI International |
And 15 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2014
Both preclinical evidence and clinical evidence suggest that α7 nicotinic acetylcholine receptor activation (α7nAChR) improves cognitive function, the decline of which is associated with conditions such as Alzheimer's disease and schizophrenia. Moreover, allosteric modulation of α7nAChR is an emerging therapeutic strategy in an attempt to avoid the rapid desensitization properties associated with the α7nAChR after orthosteric activation. We used a calcium assay to screen for positive allosteric modulators (PAMs) of α7nAChR and report on the pharmacologic characterization of the novel compound RO5126946 (5-chloro-N-[(1S,3R)-2,2-dimethyl-3-(4-sulfamoyl- phenyl)-cyclopropyl]-2-methoxy-benzamide), which allosterically modulates α7nAChR activity. RO5126946 increased acetylcholine-evoked peak current and delayed current decay but did not affect the recovery of α7nAChRs from desensitization. In addition, RO5126946's effects were absent when nicotine-evoked currents were completely blocked by coapplication of the α7nAChR-selective antagonist methyl-lycaconitine. RO5126946 enhanced α7nAChR synaptic transmission and positively modulated GABAergic responses. The absence of RO5126946 effects at human α4β2nAChR and 5-hydroxytryptamine 3 receptors, among others, indicated selectivity for α7nAChRs. In vivo, RO5126946 is orally bioavailable and brain-penetrant and improves associative learning in a scopolamine-induced deficit model of fear conditioning in rats. In addition, procognitive effects of RO5126946 were investigated in the presence of nicotine to address potential pharmacologic interactions on behavior. RO5126946 potentiated nicotine's effects on fear memory when both compounds were administered at subthreshold doses and did not interfere with procognitive effects observed when both compounds were administered at effective doses. Overall, RO5126946 is a novel α7nAChR PAM with cognitive-enhancing properties. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics. Source
Gred | Date: 2007-11-20
Read only memory blank compact discs; pre-recorded compact discs featuring music, motion pictures, music videos and musical performances. Printed matter, namely newspaper for general circulation, general interest magazines, periodicals, journals; cookbooks, picture books, account books; address books; appointment books; autograph books, check books; coupon books; general feature magazines; TV and movie magazines; computer magazines; travel magazines; sports magazines; fashion and decoration magazines; bags of paper for household use and packaging; drawing paper; notebook paper; mounted and unmounted photographs; lithographic and pictorial graphic prints; posters, placards of paper or cardboard, photograph albums, event albums, and memory books. Meat, fish, poultry and game, meat extracts, preserved, dried and cooked fruits and vegetables, jellies, jams, fruit sauces, eggs, milk; dairy products excluding ice cream; ice milk and frozen yogurt; edible oils and fats. Flour; processed cereal-based food to be used as a breakfast food, snack for or ingredient for making other foods; candy, bread, pastry, flavored ices, honey, treacle, salt, mustard, vinegar, sauces. Agricultural and plant seeds, foodstuffs for animals, live animals. Alcoholic beverages namely, wine, vodka, gin, bourbon. telecommunications, namely, providing telecommunications connections to a global computer network, telecommunications gateway services, telecommunications services namely personal communication services. Arranging of exhibitions for entertainment, sporting and cultural purposes. Restaurant services, cocktail lounge services, cafes, catering.
Germitec and Gred | Date: 2007-10-09
Recorded computer software especially in connection with using apparatus in the field of disinfecting surgical instruments, namely, recorded computer software for use in tracking, and the traceability of, the use or disinfection of probes. Printed matter, namely, user manuals and instruction manuals on using disinfection apparatus; printed matter, namely, user manuals and instruction manuals on disinfection services especially of surgical instruments.
Germitec and Gred | Date: 2007-09-04
Medical sterilization and decontamination apparatus using radiation in a germicidal atmosphere for medical use.. Non-medical sterilization and decontamination apparatus using radiation in a germicidal atmosphere for non-medical use..
Germitec and Gred | Date: 2008-02-19
Medical apparatus and instruments, namely, sterilization and disinfection units for medical purposes, sterilization and disinfection units for medical instruments and probes, ultrasonic medical diagnostic apparatus, ultrasound diagnostic apparatus, medical ultrasound apparatus; medical diagnostic imaging apparatus. Sterilizers, not for medical purposes; sterilization and disinfection units not for medical purposes, namely, disinfectant apparatus for industrial purposes and for water, air or dish treatment. Disinfection services, in particular surgical instruments.