1.Pharmacological characterization of cGMP regulation by the biarylpropylsulfonamide class of positive, allosteric modulators of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors.
Ryder JW1, Falcone JF, Manro JR, Svensson KA, Merchant KM. J Pharmacol Exp Ther. 2006 Oct;319(1):293-8. Epub 2006 Jun 27.
The biarylpropylsulfonamide class of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) potentiators represented by N-2-(4-(4-cyanophenol)phenol)propyl-2-propanesulfonamide (LY404187) and (R)-4'-[1-fluoro-1-methyl-2-(propane-2-sulfonylamino)-ethyl]-biphenyl-4-carboxylic acid methylamide (LY503430) are positive, allosteric AMPA receptor activators, which enhance AMPA receptor-mediated neurotransmission by reducing desensitization of the ion channel. Although these compounds have efficacy in in vivo rodent models of cognition, depression, and Parkinson's disease, little is known about biochemical pathways activated by these agents. Given the well established regulation of the nitric oxide/cGMP pathway by excitatory neurotransmission, the current study characterized AMPA receptor potentiator-mediated cGMP response in mouse cerebellum. Acute treatment by both LY404187 and LY503430 [2.0, 5.0, or 10 mg/kg subcutaneously (s.c.)] elevated basal cerebellar cGMP levels in a dose-dependent manner.
2.NTP technical report on the toxicity studies of Cresols (CAS Nos. 95-48-7, 108-39-4, 106-44-5) in F344/N Rats and B6C3F1 Mice (Feed Studies).
Dietz D. Toxic Rep Ser. 1991 Feb;9:1-128.
Cresols are monomethyl derivatives of phenol, and are found as constituents of coal tar, in various industrial solvents and resins, and in some essential oils. In 28-day toxicity studies, F344/N rats and B6C3F1 mice of both sexes were given o-cresol, m-cresol, p-cresol, or m/p-cresol (60:40) at concentrations from 300 ppm to 30,000 ppm in the diet. In 90-day studies, o-cresol or m/p-cresol (60:40) were added to the diet in concentrations as high as 30,000 ppm to F344/N rats and 20,000 ppm (o-cresol) or 10,000 ppm (m/p-cresol) to B6C3F1 mice. In the 28-day studies, all rats survived (5 per sex per dose), but some mice given o-cresol at 30,000 ppm, or m-cresol or p-cresol at 10,000 ppm or 30,000 ppm died before the end of the studies. Feed consumption was depressed during the first study week in all high- dose groups of animals and weight gains were generally less than controls in groups given 10,000 or 30,000 ppm in the four 28-day studies.