ANALYSIS OF SOME BENZODIAZEPINES

Abstract

Benzodiazepines are used in many areas of medicine. They are indicated in psychiatric and neurological disorders such as the treatment of anxiety, convulsions, sleep disorders, depression, . muscle spasm and alcohol withdrawal syndrome. They are also used m combination with major tranquilizers and antidepressants to • alleviate anxiety symptoms associated with schizophrenia and depression (ll_ ..

Structure - Activity Relationship (t)

The benzodiazepines emanate from a basic structure (Fig. 1 ) constituting of three rings. Various substituents have been added to develop the available analogues (table 1 ). The effects of these substituents on the biological activity have been reviewed and summarized as follows:

The 7- membered imino-lactam ring is essential for anxiolytic activity. The substitution of a methyl group at position I increase activity and larger substituents in this position decrease activity.

Generally, electron withdrawing groups (e.g. halogens, N02, CF3 ) in position 7 increase activity while electron releasing groups ( e.g. CH3, OCH3) decrease activity. Substituents in any other position in the ring A cause a decrease in activity.

' The addition of halogens at the 2' position in the phenyl ring increase activity, but addition of a substituent at 4' very strongly decreases the activity. Study of the structure activity relationships has also revealed that \ a 7-nitro group, as in clonazepam, enhances anti con vu I sent potency and