Nonbenzodiazepines: Drug Information Page

Fast Facts: 

Also known as the 'Z' Drugs or the 'benzodiazepine-like drugs'.

Class of centrally acting depressants with a distinct chemistry but similar pharmacology to the benzodiazepines. Z-drug is to benzodiazepine as opioid is to opiate, (or fentanyl to morphine).

Currently 2 which are widely used in the US - Zolpidem (i.e. Ambien, Ambien CR) and eszopiclone (Lunesta).

Like benzodiazepines, Z drugs target the benzodiazepine subtype of the GABA-a receptor complex, exerting a braking effect on excitatory neuro-transmission and leading to a calming affect on a given portion of the brain.

Limited information exists as to the development of tolerance, dependence, and long term effects of nonbenzodiazepines compared to benzodiazepines. However, one can assume they are similar in these respects.

Z drugs are most often used as prescription sleep aids. They are now often preferred to benzodiazepines in the treatment of insomnia & related sleep disorders.

The first to appear were zopiclone, zolpidem, and zaleplon; all three are used as sleep aids.

Side effects are similar to benzodiazepines and include hypnosis, anterograde amnesia, skeletal muscle relaxation, depression, ataxia and cognitive impairment.

Some Z-drugs have been known to produce bizzarre side effects such as hallucinations or even fugue states; characterized by sleepwalking, talking, driving, cooking and performing other complex tasks while not awake, with no recollection of the events afterward. This has been common with zolpidem in particular and has made Ambien a popular recreational drug in some circles.

Recent research & development has focused on a class of nonbenzodiazepine derivatives for anxiolytic use. These compounds possess anti-anxiety properties of the benzodiazepines and nonbenzodiazepines but produce little to no hypnosis or intoxication at therapeutic doses. For instance, pagoclone binds with benzodiazepine receptors with extreme selectivity, targeting the GABA a2 and a3 subtype without affecting the a1 subtype - the a2 and a3 subtypes mediate the anxiolytic effects of benzodiazepine-type drugs, while the a1 subtype mediates sedation & memory loss.

Benzodiazepine structure (far right) VS Nonbenzodiazepine structure (first 3 on the left)