title: New bicyclic antidepressant agent. Synthesis and activity of napactadine and related compounds.
abstract: A number of N,N'-dialkylarylamidines were synthesized and evaluated for antidepressant activity. Several of these compounds were synthesized from the corresponding nitriles by a new method. Slight structural modification in the series caused a marked change in biological activity and led to compounds as active as imipramine. The arylacetamidine, N,N'-dimethyl-2-naphthaleneethanimidamide hydrochloride (33) (napactadine) was selected for clinical study. Forty-eight additional analogues of 33, including a number of N-alkylamidines, were prepared.
mesh_terms: D000374:Aggression / Q000187:drug effects; D000578:Amidines / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001763:Blepharoptosis / Q000139:chemically induced; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D003863:Depression / Q000188:drug therapy*; D004341:Drug Evaluation; D004357:Drug Synergism; D004558:Electric Stimulation; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012110:Reserpine / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000578:Amidines; D015016:Yohimbine; C047240:napactadine; D012110:Reserpine; D009638:Norepinephrine