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Zopiclone (RP 27 267) is an hypnotic with a chemical structure different from that of the benzodiazepines (BZD) or barbiturates. Studies of zopiclone in classical psycho-pharmacological tests, in comparison with BZD and barbiturates, have shown that it exhibits the five main types of activity considered as characteristic of the pharmacological profile of BZD and partly of that of barbiturates (anticonvulsant, myorelaxant, antiaggressive, sedative-hypnotic and ‘anticonflict’). However, like BZD, zopiclone differs from barbiturates by a high safety margin. Electrophysiological studies performed in cats have shown that zopiclone induces modifications in sleep-wakefulness pattern which are close to those observed with BZD, specially with nitrazepam. Moreover, zopiclone increases the threshold for arousal by reticular formation stimulation, rather more than nitrazepam, but with a shorter duration of action. The short duration of action of zopiclone has been demonstrated in other species using different tests.

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Abstract.-A sustained increase in the turnover of norepinephrine coupled with an increased concentration of that amine has, in a previous study, been observed in the brains of rats exposed to electroconvulsive shock twice daily for one week. The phenomenon has been further examined by studying the effects of a similar regimen of electroconvulsive shock upon tyrosine hydroxylase in the brain, since that enzyme appears to be rate-limiting in norepinephrine synthesis. A small (15%) but significant increase in the whole brain enzyme activity was found in the electroshock-treated animals. A significant increase of tyrosine hydroxylase activity was found in the brainstem (24%) and cortex (20%) of such animals.Chronic electroconvulsive shock induces a sustained increase in the synthesis and utilization of norepinephrine in different parts of the rat central nervous system:' (a) brainstem and mesencephalon, (b) telencephalon and diencephalon, and (c) spinal cord. Since these changes in norepinephrine are observed 24 hours after the end of the electroconvulsive shock treatment, it was decided to examine the possibility that the acceleration of norepinephrine synthesis could be related to an increase in the activity of tyrosine hydroxylase which appears to be the rate-limiting enzyme in norepinephrine synthesis.Methods.-Male albino rats (Charles River Strain), approximately 275 gm in weight, were randomly divided into two groups: One of these groups was subjected to electroconvulsive shock for 7 days by the method employed previously;' the other was treated similarly, even to application of electrodes, except that the current was not turned on. The rats were decapitated 24 hr after the last period of electroconvulsive shock or "sham shock." The whole brain was quickly removed and frozen or dissected in the cold. The following regions were isolated: (a) brainstem and mesencephalon, (b) hypothalamus, (c) thalamus, (d) cortex, and (e) caudate nuclei. The tissues were then frozen and kept in dry ice until tyrosine hydroxylase was determined, between 36 hr and 3 days after decapitation. Freezing and storage for 3 days was found not to alter the activity of rat brain tyrosine hydroxylase.Partial purification and determination. of tyrosine hydroxylase: All the samples in experiment 1 (whole brain) and the samples corresponding to the same brain region (experimental and control) in experiment 2 were processed at one time, following a random order to minimize time effects. The frozen tissues were weighed and homogenized in 10 ml of ice-cold distilled water; larger amounts of tissue (cortex and the whole brain) were homogenized in 20 ml. All procedures were performed at 4VC unless otherwise stated.The homogenate was transferred to a polycarbonate centrifuge tube, balanced by the addition of water, and centrifuged at 100,000 X g for 1 hr. The supernatant was transferred to a 50-ml plastic centrifuge tube, and 7 ml (14 ml for the cortex and whole brain) of a saturated solution of ammoniuml sulfate were added while the mixture was bei...

Suriclone (RP 31,264), like zopiclone (RP 27,267), belongs to the family of cyclopyrrolones and is chemically entirely different from the benzodiazepines (BZDs). However, it possesses a pharmacological profile close to that of the BZDs and proved to be useful in therapeutics as an anxiolytic agent. In the present paper it is shown that suriclone possesses a high affinity for flunitrazepam binding sites and that tritiated suriclone binds specifically with high affinity in rat hippocampus (KD = 0.44 +/- 0.03 nM) and rat cerebellum (KD = 0.53 +/- 0.12 nM). Further, suriclone binding sites are recognized by BZDs or zopiclone, similarly in the two regions. The affinities of four BZD derivatives--nitrazepam, flunitrazepam, diazepam, and chlordiazepoxide--are similar for suriclone and flunitrazepam binding sites. Suriclone binding sites are, like flunitrazepam sites, protected from thermal inactivation by gamma-aminobutyric acid (GABA) (10 microM), but only flunitrazepam binding is enhanced by GABA. It could be postulated from this that suriclone interacts with a subpopulation of receptors that might be modulated differently from flunitrazepam binding sites. Our results indicate that suriclone could be a new probe for investigating the so-called BZD receptors.