THE MECHANISM OF ACTION AND PHARMACOLOGY OF ZOPICLONE

Development of new hypnotics with fewer unwanted effects has a high pr iority. The cyclopyrrolone derivative zopiclone has shown potent sedat ive hypnotic properties in humans. Zopiclone is chemically unrelated t o the 1,4-benzodiazepines. However, its pharmacological profile is clo sely related to that of the 1,4-benzodiazepines. Zopiclone, like benzo diazepines, potentiates the function of gamma-aminobutyric acid (GABA) at the GABA(A) receptor complex. Results of various radioligand bindi ng studies indicate that there are subtle differences in the molecular interaction of zopiclone and benzodiazepines with the GABA(A) recepto r. Probably, zopiclone interacts with a site which is different from, but closely associated with, the benzodiazepine binding site within th e GABA(A) receptor complex. The animal behavioural pharmacological pro perties of zopiclone are qualitatively similar to those of the benzodi azepines; zopiclone exerts sedative-hypnotic, anticonvulsant, muscle r elaxant, antiaggressive and anticonflict actions in experimental anima ls. The sedative-hypnotic, anticonflict and antiaggressive actions are comparable to those of most benzodiazepines, whereas anticonvulsant a nd muscle relaxant effects seem to be weaker than those induced by ben zodiazepines. Zopiclone has a high margin of safety. The short duratio n of action of zopiclone is favourable for a hypnotic. Based on bioche mical and behavioural data, zopiclone may have an advantageous side-ef fect profile, especially regarding tolerance/physical dependence liabi lity.