The invention provides compounds, compositions and methods for inhibiting th e glycine transporter (2) and for affecting glycine transporter mediated neuronal activity. Useful compounds comprise compounds of Formula I : wherei n n is (0, 1, 2 or 3) and R is independently halogen, hydroxy, lower alkyl optionally substituted with halogen or lower alkoxy optionally substituted with halogen ; X is O, S or N-R' (wherein R's is lower alkyl, aryl, heteroaryl, aryl-lower alkylene or heteroaryl-lower alkylene) ; Q may be absent or present, and when present, it is represented by the formula : in which n, R and X are as defined above ; when Q is present, W is a lower alkylene and when Q is absent, W is optionally substituted lower alkyl, optionally substituted aryl, optionally substituted heteroaryl (optionally substituted aryl)-X-CH2-or (optionally substituted heteroaryl)-X-CH2-in whic h X is as defined above ; or a pharmaceutically acceptable salt thereof. These compounds are particularly useful for treating diseases of the nerve and muscle, including psychoses, pain, epilepsy, neurodegenerative diseases, stroke, head trauma, multiple sclerosis and the like, and of muscle disorder s, including diseases or conditions associated with increased muscle contractio n, such as spasticity and myoclonus. In addition, the compounds may be used to discover other agents with improved activity in assays in which the compound s of the invention are active.
HETEROCYCLIC INHIBITORS OF GLYCINE TRANSPORTER 2