Julie Cianfrogna

TL;DR: It appears that most CNS-active agents demonstrate at least some P-gp-mediated transport that can affect brain concentrations, and unbound plasma concentrations may need to be greater than values projected using receptor affinity data to achieve adequate receptor occupancy for effect.

TL;DR: The discovery of a new class of PDE10A inhibitors exemplified by TP-10 (2-{4-[-pyridin-4-yl-1-(2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-phenoxymethyl}-quinoline succinic acid), an agent with greatly improved potency, selectivity, and pharmaceutical properties is described.

TL;DR: The present study demonstrates that rapid brain equilibration requires a combination of high BBB permeability and low brain tissue binding, and the strategy to select compounds with rapid brain Equilibration in drug discovery should identify compounds with highBBB permeable and low nonspecific binding in brain tissue.

TL;DR: For quick brain penetration with simple diffusion mechanism compounds, CCSF and Cu,plasma represent Cu,brain equally well; for efflux substrates or slow brain penetration compounds,CCSF appears to be equivalent to or more accurate than Cu, Plasma to representCu,brain.

TL;DR: It is suggested that inhibition of CKIϵ yields a perturbation of oscillator function that forestalls light as a zeitgeber, and it is demonstrated that pharmacological tools such as PF-670462 may yield valuable insight into clock function.