NAME OF DRUG
(zopiclone)Tablets, 5.0 mg and 7.5 mgHypnotic and Sedative
ACTIONS, CLINICAL PHARMACOLOGY
IMOVANE (zopiclone), a cyclopyrrolone derivative, is a short-acting hypnotic agent.IMOVANE belongs to a novel chemical class, which is structurally unrelated to existinghypnotics. However, the pharmacological profile of IMOVANE is similar to that of thebenzodiazepines.IMOVANE pharmacological properties are: hypnotic, sedative, anxiolytic, anti-convulsant,muscle-relaxant. These effects are related to a specific agonist action at central receptorsbelonging to the GABAa macromolecular complex, modulating the opening of thechloride ion channel.In sleep laboratory studies of one to 21-day duration in man, zopiclone reduced sleeplatency, increased the duration of sleep and decreased the number of nocturnalawakenings. Zopiclone delayed the onset of REM sleep but did not reduce consistentlythe total duration of REM periods. The duration of stage 1 sleep was shortened, and thetime spent in stage 2 sleep increased. In most studies, stage 3 and 4 sleep tended to beincreased, but no change and actual decreases have also been observed. The effect ofzopiclone on stage 3 and 4 sleep differs from that of the benzodiazepines, whichsuppress slow wave sleep. The clinical significance of this finding is not known.With hypnotic drugs, the duration of hypnotic effect and the profile of unwanted effectsmay be influenced by the alpha (distribution) (t½
) and beta (elimination) (t½
) half-livesof the administered drug and any active metabolites formed. When half-lives are long, thedrug or metabolite may accumulate during periods of nightly administration and beassociated with impairments of cognitive and motor performance during waking hours. Ifhalf-lives are short, the drug and metabolites will be cleared before the next dose isingested, and carry-over effects related to sedation or CNS depression should be minimalor absent. If the drug has a very short elimination half-life, it is possible that a relativedeficiency (i.e., in relation to the receptor site) may occur at some point in the intervalbetween each night’s use. This sequence of events may account for two clinical findingsreported to occur after several weeks of nightly use of rapidly eliminated benzodiazepinesor benzodiazepine-like hypnotics: 1) increased wakefulness during the last third of thenight and 2) the appearance of increased day-time anxiety (see WARNINGS).