Tricyclics with analgesic and antidepressant activity. 1. [[(Alkylamino)ethyl]thio]dibenz[b,f]oxepins and 10,11-dihydro derivatives.
A series of [[(alkylamino)ethyl]thio]dibenz[b,f]oxepins (I) and their 10,11-dihydro derivatives (II) was synthesized and subjected to broad analgesic/CNS screening. Several analogues of both types, carrying small N-substituents and frequently a nuclear fluorine function, have been found to possess potent analgesic activity in the phenylquinone writhing assay (PQW) and the tail-flick test in mice. Many of these compounds also exhibited significant activity in antagonizing tetrabenazine-induced ptosis, as exemplified by 10b, 16b, and 18b. 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 did not produce tolerance in mice following chronic administration in the PQW screen.
D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic / Q000138:chemical synthesis*; D014150:Antipsychotic Agents; D055598:Chemical Phenomena; D002621:Chemistry; D003990:Dibenzoxepins / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice
D000700:Analgesics; D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D003990:Dibenzoxepins; D000661:Amphetamine