Novel analogs of tricyclic psychopharmacological agents.
The synthesis of several novel analogs of amitriptyline and chlorprothixene, in a number of which the position of the side-chain nitrogen atom rigidly fixed with respect to the tricyclic nucleus, is described. The compounds were evaluated for antidepressant-like activity in the Dopa and serotonin interaction tests and for potential antipsychotic activity in the methamphetamine interaction test. 5-(3-Dimethylaminocyclohex-1-enyl)-5H-dibenzo[a,d]cycloheptene (12) was about equipotent with imipramine in the Dopa and methamphetamine tests, and 3-chloro-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-spiro-6'-3'-methyl-3'-azabicyclo[3.1.0]hexane (23) also displayed marked activity in the same tests. Prototype compounds for other ring systems, 3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene tropane (16) and 5-(3-dimethylaminocycloheptylidene)-10,11-dihydro-5H-dibenzo[a,d]cycloheptene (18), were less active.
D000639:Amitriptyline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000138:chemical synthesis*; D002749:Chlorprothixene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D004347:Drug Interactions; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D012701:Serotonin / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D000639:Amitriptyline; D012701:Serotonin; D008694:Methamphetamine; D004295:Dihydroxyphenylalanine; D002749:Chlorprothixene