Structure-activity studies on antidepressant 2,2-diarylethylamines.
A series of 2,2-diarylethylamine derivatives has been examined for potential antidepressant activity in the tetrabenazine (TBZ) test. Diethanolamine 4 (McN-4187) was one of the more potent compounds despite its polar alcohol functionalities [ED50 values of 15 mg/kg (exploratory activity) and 1.5 mg/kg (ptosis)]. Structure-activity relationships are described. Minor structural modifications of 4 were sufficient to strongly attenuate activity. For example, changing one phenyl group to a 2-thienyl, cyclohexyl, or 3,4-dimethoxyphenyl group greatly reduced activity. Replacing both phenyl groups by 4-chlorophenyl groups also dissipated activity. The bisethanol functionality was not essential for activity (q.v. 17-19 in Table I). Although 17-19 compared well with 4 in the TBZ assay, only 19 (like 4) showed a satisfactory profile in the maximal electroshock seizure threshold test.
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004597:Electroshock; D004983:Ethanolamines / Q000494:pharmacology*; D005021:Ethylamines / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D013329:Structure-Activity Relationship; D013747:Tetrabenazine / Q000037:antagonists & inhibitors
D000928:Antidepressive Agents; D004983:Ethanolamines; D005021:Ethylamines; C020283:diethanolamine; D013747:Tetrabenazine