A 20 year-old patient presented with schizophrenia which was associated with Klippel-Feil syndrome and flat foot.

The mechanisms of action which account for the effectiveness of clozapine as a pharmacotherapy for the treatment of neuroleptic non-responders and neuroleptic intolerant schizophrenic subjects remain elusive. We review recent data concerning the actions of clozapine in laboratory animals, and discuss the likely sites of action of clozapine and the receptors through which clozapine acts. We suggest that actions at dopamine D2 receptors in the caudate nucleus and putamen underlie the extrapyramidal side effects of conventional neuroleptics. In contrast, we propose that clozapine acts in the prefrontal cortex, specifically targeting an as yet unidentified DA receptor of the D2 family, to exert therapeutic actions in neuroleptic non-responders. We suggest that the ability of clozapine to augment extracellular dopamine levels in the prefrontal cortex may represent a key mechanism contributing to the therapeutic effects of this drug, and suggest some alternative approaches which might be expected to result in effects similar to those of clozapine.

The effect of zopiclone (7.5 mg) on attention, vigilance and memory components was evaluated during a nocturnal period in comparison to a placebo, to zolpidem (10 mg) and to flunitrazepam (1 mg) in a double blind, randomized study, after administration of a single dose in 16 young healthy volunteers. It appears that there is a clear effect on attention and vigilance; this effect is apparent during the kinetic phase of the absorption of the medication. The effect on memory is transient and is absent four hours after the ingestion of the drug. The objective results are not strictly consistent with the chronology of the subjective parameters (Leeds scale — Visual Analogue Scale). The three hypnotics under comparison do not fundamentally differ except in their kinetic/pharmacodynamic effect relationship. One important fact, taking the parameters as a whole, is that there is no objective “residual” effect.

Before and after its introduction in 1987, zopiclone was the object of investigation in 16 psychometric studies employing both healthy volunteers and insomniac patients. Their common purpose was to determine whether nocturnal doses (usually the standard 7.5 mg) possess residual sedative effects that interfere with skilled safety-relevant performance, such as car driving, over the following day. Most studies have found no residual effects. Those that did, have shown them to be modest in magnitude and not to persist for longer than about 12 hours from the time of dosage. Without altering the general conclusion that zopiclone possesses few if any residual effects of clinical relevance, it must be said that the studies reviewed failed to meet current methodological standards and may have left some important questions unanswered.