A series of 4-substituted 10H-theino[2,3-b][1,5]benzodiazepines has been synthesized. These compounds have been assessed for their ability to block a conditioned avoidance response (CAR) and to produce catalepsy in rats and have been compared with several typical and atypical neuroleptics. The compounds which inhibit CAR at doses which produce no catalepsy are believed to cause less extrapyramidal side effects in the clinic. A number of compounds (9, 12, 17, 29, and 34) show potent neuroleptic activity, yet maintain a favorable separation of activity on these two parametrs. Three 5-piperazinyl-10H-thieno[2,3-b][1,4]benzodiazepine derivatives (46-48) analogous to compounds in the [1,5] series have been prepared for comparison and were found to be inactive.

Animals were administered increasing doses of morphine for 16 days. During withdrawal they were challenged with an apomorphine ester or lergotrile. These dopamine agonists produced quantitatively different effects on behaviour. The results suggest that chronic morphine administration leads to dopamine supersensitivity which may be anatomically distinct in origin.

AbstractAus dem Cyclohexadien (I) und den isomeren Nitrilen (IIa) bzw. (IIb) werden die Cyanbicyclooctane (IIIa) bzw. (IIIb) synthetisiert, deren Reduktionsprodukte (IVa) bzw. (IVb) zu den Dimethylaminoderivaten (Va) bzw. (Vb) umgesetzt RI werden; die analog (IV) synthetisierten Aminomethylbicyclooctane (VI) werden nach einer modifizierten Eschweiler‐Clarke‐Methode zu den Derivaten (VII) N,N‐dimethyliert Die trans‐Diels‐Alder4Addukte (IX) ‐ zugänglich aus (I) und den trans‐Zimtaldehyden (VIII) ‐ werden durch Bromierung/Dehydrobromierung in die ungesättigten Aldehyde (X) übergeführt; Kondensation der Aldehyde (X) mit Methylamin gibt die entsprechenden Imine, die zu den sek. Aminen (XI) reduziert werden; diese lassen sich analog (VI) zu den tertiären Aminen (XII) umsetzen.