[CAS NO. 871362-31-1]  CTEP (RO4956371)

CTEP is significantly active at doses of 0.1 mg/kg and 0.3 mg/kg in treatment of anxiety in mouse. CTEP significantly increases drinking time at doses of 0.3 mg/kg and 1.0 mg/kg in the Vogel conflict drinking test in rat, whereas it has no effect at lower doses. The half-life of CTEP (oral) is 18 h, and the B/P ratio based on total drug concentrations in plasma and whole brain homogenates is 2.6 in mice. After single oral doses of 4.5 and 8.7 mg/kg CTEP formulated as microsuspension in a saline/Tween vehicle administrated to adult C57BL/6 mice is rapidly absorbed and achieves close to maximal exposure after approximately 30 min. Chronic administration in adult mice with a dose of 2 mg/kg p.o. every 48 h for 2 months reaches a minimal CTEP brain exposure of 240 ng/g. CTEP fully displaces [H]ABP688 in mouse brain regions known to express mGlu5, and 50% displacement is achieved with doses producing an average compound concentration of 77.5 ng/g measured in whole brain homogenate. CTEP (2 mg/kg p.o. bid) achieves uninterrupted mGlu5 occupancy per 48 hours in mice. CTEP (2 mg/kg p.o.) treatment corrects elevated hippocampal long-term depression, excessive protein synthesis, and audiogenic seizures in the Fmr1 knockout mouse.