Discovery of novel modulators of metabotropic glutamate receptor subtype-5.

A series of potent and selective mGluR5 antagonists were synthesized and evaluated in vitro and in vivo. It was found that a pyridyl functionality is a potential replacement for acetonitrile in the lead structure, with 2-pyridyl being most favored. Additionally, the benzoxazole moiety could also be replaced by other heterobicyclic rings such as imidazothiazole.

GABA-A and 5-HT1A receptor agonists block expression of fear-potentiated startle in mice.

The present experiments characterized the acquisition of fear-potentiated startle (FPS) and determined the sensitivity of FPS to anxiolytic compounds in DBA/1J mice. A light (30 s) conditioned stimulus (CS) and mild footshock (0.14 mA, 0.