Pharmacological properties and mechanism of action of the cyclopyrrolones. 1992

J M Stutzmann, and O Piot, and M Reibaud, and A Doble, and J C Blanchard
Biology Department, Rhone Poulenc Rorer, Vitry-sur-Seine.

We present the pharmacological properties of two cyclopyrrolones, zopiclone as a hypnotic and suriclone as an anxiolytic, and examine their mechanism of action. The effects of zopiclone on the amount of time spent at each vigilance level have been studied in freely moving rats. Zopiclone from 2.5 mg/kg i.p. extends the duration of slow wave sleep (SWS), concomitantly shortening the periods awake. This SWS inducing effect of zopiclone was more potent after 10 mg/kg i.p.; moreover, zopiclone did not depress REM sleep and no rebound of activity in wakefulness or REM sleep were observed the day after zopiclone treatment. In rats, at the cortical level, zopiclone increases the spectral energy in the delta band (0.5 to 4 hertz). This rise in energy appears at doses starting from 1.25 mg/kg p.o. and can also reach the fast frequencies (beta band: 12 to 16 hertz). This power spectrum is characteristic of a compound having tranquilizing-hypnotic potential. Taken together these EEG results corroborate the clinical studies. In man, zopiclone increased SWS, decreased SWS latency and respected sleep architecture in both healthy volunteers and insomniacs. This respect of sleep structure and the relative short duration of action of zopiclone minimized the residual effects seen upon waking (drowsiness, impairment of psychomotor performance). In the Geller-Seifter test, an operant conflict procedure, the minimal effective dose (MED) of suriclone in reversing the conflict-induced inhibition of drinking behavior was 2.5 mg.kg-1 p.o. in rats. Depression of unpunished responding is only seen at higher doses (20 mg.kg-1 p.o.).(ABSTRACT TRUNCATED AT 250 WORDS)

UI MeSH Term Description Entries
D006993 Hypnotics and Sedatives Drugs used to induce drowsiness or sleep or to reduce psychological excitement or anxiety. Hypnotic,Sedative,Sedative and Hypnotic,Sedatives,Hypnotic Effect,Hypnotic Effects,Hypnotics,Sedative Effect,Sedative Effects,Sedatives and Hypnotics,Effect, Hypnotic,Effect, Sedative,Effects, Hypnotic,Effects, Sedative,Hypnotic and Sedative
D009287 Naphthyridines A group of two-ring heterocyclic compounds consisting of a NAPHTHALENES double ring in which two carbon atoms, one per each ring, are replaced with nitrogens.
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D011963 Receptors, GABA-A Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop. Benzodiazepine-Gaba Receptors,GABA-A Receptors,Receptors, Benzodiazepine,Receptors, Benzodiazepine-GABA,Receptors, Diazepam,Receptors, GABA-Benzodiazepine,Receptors, Muscimol,Benzodiazepine Receptor,Benzodiazepine Receptors,Benzodiazepine-GABA Receptor,Diazepam Receptor,Diazepam Receptors,GABA(A) Receptor,GABA-A Receptor,GABA-A Receptor alpha Subunit,GABA-A Receptor beta Subunit,GABA-A Receptor delta Subunit,GABA-A Receptor epsilon Subunit,GABA-A Receptor gamma Subunit,GABA-A Receptor rho Subunit,GABA-Benzodiazepine Receptor,GABA-Benzodiazepine Receptors,Muscimol Receptor,Muscimol Receptors,delta Subunit, GABA-A Receptor,epsilon Subunit, GABA-A Receptor,gamma-Aminobutyric Acid Subtype A Receptors,Benzodiazepine GABA Receptor,Benzodiazepine Gaba Receptors,GABA A Receptor,GABA A Receptor alpha Subunit,GABA A Receptor beta Subunit,GABA A Receptor delta Subunit,GABA A Receptor epsilon Subunit,GABA A Receptor gamma Subunit,GABA A Receptor rho Subunit,GABA A Receptors,GABA Benzodiazepine Receptor,GABA Benzodiazepine Receptors,Receptor, Benzodiazepine,Receptor, Benzodiazepine-GABA,Receptor, Diazepam,Receptor, GABA-A,Receptor, GABA-Benzodiazepine,Receptor, Muscimol,Receptors, Benzodiazepine GABA,Receptors, GABA A,Receptors, GABA Benzodiazepine,delta Subunit, GABA A Receptor,epsilon Subunit, GABA A Receptor,gamma Aminobutyric Acid Subtype A Receptors
D004569 Electroencephalography Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. EEG,Electroencephalogram,Electroencephalograms
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001007 Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with ANXIETY DISORDERS. Angst,Anxiousness,Hypervigilance,Nervousness,Social Anxiety,Anxieties, Social,Anxiety, Social,Social Anxieties
D012890 Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Sleep Habits,Sleeping Habit,Sleeping Habits,Habit, Sleep,Habit, Sleeping,Habits, Sleep,Habits, Sleeping,Sleep Habit
D013457 Sulfur Compounds Inorganic or organic compounds that contain sulfur as an integral part of the molecule. Sulfur Compound,Compound, Sulfur,Compounds, Sulfur

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