Conformationally restricted phenothiazine neuroleptics. 1. 3-(Dimethylamino)-1,2,3,4-tetrahydroazepino[3,2,1-kl]phenothiazine.
A rigid analogue of promazine, 3-(dimethylamino)-1,2,3,4-tetrahydroazepino[3,2,1-kl]phenothiazine (1), was prepared by reductive amination of the corresponding ketone 4. An X-ray crystallographic study revealed that the seven-membered ring of the hydrochloride salt of 1 exists as a half-chair-like form with the dimethylammonium group in an equatorial-like conformation. Compound 1 was approximately one-half as active as promazine as an inhibitor of [3H]spiperone binding in rat corpus striatal homogenates. In homogenates obtained from calf caudate tissue, however, 1 was only about one-twentieth as active as promazine as an inhibitor of [3H] spiperone binding. As a stimulator of homovanilic acid (HVA) synthesis in rat corpus striatum in vivo, it was about one-tenth as active as promazine.
D000818:Animals; D014150:Antipsychotic Agents / Q000138:chemical synthesis*; D002417:Cattle; D002421:Caudate Nucleus / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008958:Models, Molecular; D008968:Molecular Conformation; D010640:Phenothiazines; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D013134:Spiperone / Q000378:metabolism; D013329:Structure-Activity Relationship
D014150:Antipsychotic Agents; D010640:Phenothiazines; D011954:Receptors, Dopamine; D013134:Spiperone; D006719:Homovanillic Acid