Tricyclics with analgesic and antidepressant activity. 1. [[(Alkylamino)ethyl]thio]dibenz[b,f]oxepins and 10,11-dihydro derivatives

Abstract

A series of [[(alkylamino)ethyl]thio]dibenz[b,f]oxepins and their 10,11-dihydro derivatives was synthesized and subjected to broad analgesic/CNS screening. Several analogs of both types, carrying small N-substituents and frequently a nuclear F function, had potent analgesic activity in the phenylquinone writhing assay (PQW) and the tail-flick test in mice. These compounds exhibited significant activity in antagonizing tetrabenazine-induced ptosis. Results from the mouse jumping test indicated low physical dependence potential for these compounds, and further evidence for a nonnarcotic profile was provided by the absence of significant naloxone interactions with the tail-flick response. Compound 10b [10-[[.beta.-(methylamino)ethyl]thio]dibenz[b,f]oxalate] did not produce tolerance in mice following chronic administration in the PQW screen.