Tricyclics with analgesic and antidepressant activity. 2. [[(Alkylamino)ethyl]thio]dibenzo[b,f]thiepins and 10,11-dihydro derivatives.
A series of [[(alkylamino)ethyl]thio]dibenz[b,f]thiepins (III) and their 10,11-dihydro derivatives (IV) was synthesized and subjected to broad analgesic/CNS screening. Preliminary results indicated a combination of analgesic/antidepressant profiles, similar to that observed for the [[(alkylamino)ethyl]thio]dibenz[b,f]oxepins (I) and their corresponding dihydro derivatives (II). The most active congener from the present series, 10b, shows an antinociceptive potency in the pentazocine range as assessed by phenyl-p-quinone-induced writhing (PQW) and tail flick in mice. It is also more than twice as active as imipramine in preventing tetrabenazine-induced ptosis (TBZ), a test widely recognized to be of predictive value for clinically efficacious antidepressants.
D006916:5-Hydroxytryptophan / Q000037:antagonists & inhibitors; D000661:Amphetamine / Q000037:antagonists & inhibitors; D000700:Analgesics / Q000138:chemical synthesis*; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000138:chemical synthesis*; D014150:Antipsychotic Agents / Q000138:chemical synthesis; D001058:Apomorphine / Q000037:antagonists & inhibitors; D016227:Benzoquinones; D001763:Blepharoptosis / Q000517:prevention & control; D055598:Chemical Phenomena; D002621:Chemistry; D003988:Dibenzothiepins / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008297:Male; D011809:Quinones / Q000037:antagonists & inhibitors; D051381:Rats; D013239:Stereotyped Behavior / Q000187:drug effects
D000700:Analgesics; D000929:Antidepressive Agents, Tricyclic; D014150:Antipsychotic Agents; D016227:Benzoquinones; D003988:Dibenzothiepins; D011809:Quinones; C029322:phenylbenzoquinone; D006916:5-Hydroxytryptophan; D000661:Amphetamine; D001058:Apomorphine