1,4-Benzodiazepines. VIII - Central depressive activity and spasmolytic action of isoquino-[2,1-d] [1,4] benzodiazepines. Structure-activity relationships.

The pharmacological activity of four new groups of isoquino [2,1-d] ((1,4]benzodiazepines, i.e. the 6-oxo-12,13-dimethoxy-5H-7H--9,10-dihydroisoquino [2,1-d] [1,4]benzodiazepinium bromides (I); 5,9,10,14b--tetrahydroisoquino [2,1-d] [1,4]benzodiazepin-7H-6-ones (II); 6-phenyl-12,13--dimethoxy-7,9,10,14b-tetrahydroisoquino [2,1-d] [1,4]benzodiazepines (III) and 6-phenyl-12,13-dimethoxy-7H-9,10-dihydroisoquino [2,1-d] [1,4]benzodiazepinium bromides (IV) was studied. All the compounds studied are biologically active. They show a depressive effect on the central nervous system, which is most pronounced in (II). It was established that the presence of alkyl substituents in the position-7 of the structure (II) as well as the chlorine atom in position-2 resulted in an increase of activity. Most of these compounds possess a mild or strong antinociceptive effect. Some of them exhibited an antireserpine activity as well. The spasmolytic effect of (IV) was strong while the rest of the compounds exerted a very weak spasmolytic effect. All the compounds tested on the autonomous nervous system possess the characteristics of weak sympathomimetics.