Thiepine

Abstract: The data on the synthesis and properties of furazan derivatives fused with pyridine, pyran, thiopyran, azepine and thiepine rings are surveyed and described systematically. The bibliography includes 85 references.

Abstract: 2-Chloro-11-(2-dimethyl-aminoethoxy)dibenzo [b,f]thiepine (zotepine) is a new neuroleptic drug with a chemical structure different from known neuroleptics. The psychopharmacological effects of zotepine in mice, rats and dogs were studied and compared with those of commercially available neuroleptics. Haloperidol and perphenazine were the most active and thioridazine was the least active in hibiting apomorphine-induced gnawing and circling movement, methamphetamine-induced gnawing and circling movement, conditioned avoidance response, motor activity, dopamine-induced pancreatic secretion and apomorphine-induced vomiting. These drugs also had the same order of potency in inducing catalepsy and increasing dopamine turnover and prolactin release. Chlorpromazine, propericiazine and thiothixene were intermediate in potency. Zotepine equalled chlorpromazine in most activities, however, it was clearly less active than chlorpromazine in potentiation of barbiturate sleep and cardiovascular effect.

Abstract: The invention herein relates to novel quaternary 6,11-dihydro-dibenzo-[b,e]-thiepine-11-N-alkylnorscopine ethers, the preparation thereof, and their use as spasmolytics or bronchospasmolytics.

Abstract: The absorption, distribution, metabolism and excretion of 2-chloro-11-(2-dimethylaminoethoxy)dibenzo [b,f]thiepine (zotepine), a new neuroleptic agent, were investigated in rat, mouse, dog and man. Zotepine was absorbed rapidly and almost completely from the gastrointestinal tract in all species after oral dosing. The serum level of the unchanged drug in man was comparatively higher than in animals. The serum half-lives of zotepine after i.v. dosing were approximately 3.2 h in rats, 1.5 h in mice and 3.0 h in dogs. The drug and radioactive metabolites were rapidly distributed to the tissues of rats and mice, and the brain levels of the unchanged drug were about 20 to 30 times higher than the serum levels. Only small amounts of the unchanged drug were excreted in the urine in all species; faecal excretion through the bile was the main route of elimination of the drug and metabolites. Extensive biliary excretion and enterohepatic circulation of the radioactive compound were observed in rats. Zotepine was well metabolized in the body. Besides N-demethylation and oxygenation of the N and/or S atoms, hydroxylation of the aromatic ring and consecutive conjugation were important metabolic pathways of zotepine.