GW842166X

rat model of neuropathic pain

GW842166X has finished phase I study in healthy subjects to investigate the distribution of GW842166X in the brain.

15 mg/kg

saline

GW842166X shows similar potency and efficacy for rat and human recombinant CB2 receptors with EC50 of 91 nM and 63nM, respectively., [1] GW-842166X exhibits full agonist potency with an EC50 of 133 nM and Emax of 101% in cyclase assays. GW-842166X exhibits weak agonist potency with an EC50 of 7.780 uM and Emax of 84% in FLIPR assays. [2]

Determination of cannabinoid CB2 Receptor Agonist Activity, GW842166X is prepared as 10 mM stocks in DMSO. EC50 values (the concentration required to produce 50% maximal response) are estimated using dilutions of between 3- and 5-fold into DMSO. GW842166X in DMSO (1% final assay volume) is transferred into black, clear bottom, microtitre plates from NUNC (96- or 384-well). Cells are suspended at a density of 0.2 OD100/ml in SC media lacking histidine, uracil, tryptophan, adenine and leucine and supplemented with 10 mM 3-aminotriazole, 0.1 M sodium phosphate pH 7.0, and 20 M fluorescein di-beta-D-glucopyranoside (FDGlu). This mixture (50 ul per well for 384-well plates, 200ul per well for 96-well plates) is added to agonist in the assay plates. After incubation at 30 C for 24 hours, fluorescence resulting from degradation of FDGlu to fluorescein due to exoglucanase, an endogenous yeast enzyme produced during agonist-stimulated cell growth, is determined using a Spectrofluor microtitre plate reader (excitation wavelength: 485nm, emission wavelength: 535nm). Fluorescence is plotted against compound concentration and iteratively curve fitted using a four parameter fit to generate a concentration effect value.

GW842166X Chemical Structure

2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO