Psychopharmacology. Supplementum最新文献

{"title":"Sleep laboratory study of lormetazepam in older insomniacs.","authors":"G W Vogel","doi":"10.1007/978-3-642-69659-6_5","DOIUrl":"https://doi.org/10.1007/978-3-642-69659-6_5","url":null,"abstract":"<p><p>Lormetazepam is a new benzodiazepine hypnotic. Previous work has indicated that lormetazepam has an intermediate to short elimination half-life, i.e. in the range of 5-15 h. Hence, in older patients, the drug should be safe and hypnotically active in doses equal to or less than the doses recommended for young adults. The present study tested this hypothesis. We studied ten healthy subjects, aged 55 and older, with both subjective and objective insomnia. Subjective insomnia was the complaint of requiring at least 45 min to fall asleep and sleeping less than six and a half hours per night. Each complaint was present on at least 50% of the nights for at least three months. Objective insomnia was measured polysomnographically and was present on at least two of the last three nights of four consecutive nights of placebo baseline. The study involved a design in which treatment was administered in a double-blind fashion. Each subject was studied for 14 consecutive nights in the sleep laboratory. The drug was administered for seven consecutive nights which were preceded by a placebo baseline and followed by a placebo period of drug withdrawal. On each laboratory night subjects were monitored by continuous, all-night conventional EEG/EOG/EMG recordings. Each laboratory morning subjects completed a questionnaire on which they rated six characteristics of their sleep on the previous night. At study entry and again at study end, each subject had a physical examination by a Board internist and clinical laboratory tests. Each laboratory morning and evening subjects had a screening physical exam and completed an 11-item hypnotic drug side-effect questionnaire and a 56-item review of medical systems questionnaire. Compared with the median baseline night, on the median drug night lormetazepam 0.5 mg significantly increased total sleep time by about 25 min. The drug's reductions of sleep latency were substantial. In addition, lormetazepam 0.5 mg significantly decreased number of awakenings. No objective evidence was found of either tolerance developing to the hypnotic efficacy of lormetazepam 0.5 mg or of rebound insomnia.</p>","PeriodicalId":77887,"journal":{"name":"Psychopharmacology. Supplementum","volume":"1 ","pages":"69-78"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17213952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are electroencephalographic and psychomotor measures sensitive in detecting residual sequelae of benzodiazepine hypnotics?","authors":"H Ott","doi":"10.1007/978-3-642-69659-6_12","DOIUrl":"https://doi.org/10.1007/978-3-642-69659-6_12","url":null,"abstract":"<p><strong>Purpose: </strong>The recent development of short-acting benzodiazepines without active metabolites calls for a differentiation between the hangover effects of long-acting (LBD) and short-acting (SBD) benzodiazepines, when used as nighttime sedatives. The question now arises as to which electrophysiological and psychometric tests can record these effects with the highest degree of sensitivity.</p><p><strong>Subjects and methods: </strong>35 healthy volunteers participated in 3 randomized double-blind placebo-controlled studies. In the first 2 studies the short-acting benzodiazepine (LORMetazepam 2 mg), the medium-acting BD (FLUNitrazepam 2 mg) and the long-acting BDs (FLURazepam 30 mg and DIAZepam 10 mg) were administered in single oral doses at bedtime. Hangover was measured in the morning hours prior to administration, and 12, 36, and either 60 h (first study) or 156 h (second study) p.a. The measurements included the pharmaco-EEG, particularly the relative power in the beta band; visual analogue scales for assessing the subjective quality of sleep, EWL-adjective check list; pegboard test and radioreceptor assay. In the third study, a single oral dose of LORM 2 mg was given and the acute sedative effects were measured by the Adaptive Pursuit Tracking Test, Pauli memory test, pegboard and Pursuit Rotor.</p><p><strong>Results: </strong>The sleep-inducing properties of all BDs could be detected quite clearly on the first night p.a. Distinct hangover effects of LBD were apparent in the pegboard test and residual effects in different beta frequency bands after the first and, to a lesser degree, second nights. Such effects were barely detectable after the SBD. The time course of the RRA plasma levels of LORM and FLUN corresponded well to that of behaviour. The correspondence for DIAZ was less clear. The pharmaco-EEG proved to be the most sensitive measure of benzodiazepine effects, followed by continuous performance measures, such as the pursuit tracking test and driving simulator. Relatively low discriminability was observed with the discontinuous psychomotor tests, such as pegboard. These results have been interpreted within a concept of \"activation theory\" and it has been concluded that benzodiazepines more likely affect higher central nervous activities, such as the level of vigilance and attention, than simple activities, such as visumotor performance.</p>","PeriodicalId":77887,"journal":{"name":"Psychopharmacology. Supplementum","volume":"1 ","pages":"133-51"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17213208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lormetazepam--plasma concentrations in volunteers following sublingual and oral dosing.","authors":"D K Luscombe","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The plasma profile of lormetazepam has been determined in sixteen clinically healthy, adult male volunteers following 1 mg lormetazepam, administered either sublingually or by the oral route. Absorption of lormetazepam was found to be rapid following both sublingual and oral administration. While a trend was observed towards a more rapid rate of absorption after sublingual dosing, statistically, there was no significant difference (p greater than 0.05) between the speed with which lormetazepam was absorbed following sublingual and oral dosing. After absorption, plasma lormetazepam levels rapidly reached mean (+/- s.d.) peak concentrations of 4.9 +/- 0.9 ng/ml and 5.2 +/- 1.7 ng/ml for the sublingual and oral routes, respectively, there being no significant difference (p greater than 0.05) between these values. Likewise, there was no significant difference (p greater than 0.05) in the times at which peak plasma levels were attained in the two groups. Furthermore, measurement of the area under each plasma concentration-time curve showed that the bioavailability of lormetazepam was the same for the two routes of administration. Elimination of lormetazepam followed a similar pattern following sublingual and oral dosing, the mean terminal half-lives being 13.0 h and 13.8 h, respectively. The findings in the present study clearly indicate that the plasma profiles of lormetazepam attained on sublingual and oral dosing are similar, indeed the pharmacokinetic characteristics of this drug appear identical being independent of its route of administration.</p>","PeriodicalId":77887,"journal":{"name":"Psychopharmacology. Supplementum","volume":"1 ","pages":"99-104"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17213956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modern trends in the investigation of new hypnotics in anaesthesia.","authors":"A Doenicke","doi":"10.1007/978-3-642-69659-6_11","DOIUrl":"https://doi.org/10.1007/978-3-642-69659-6_11","url":null,"abstract":"<p><p>Over the last 20 years standardized techniques have been employed for the investigation of intravenous hypnotics, psychotropic and neuroleptic drugs. Sleep has been studied with the help of EEG measures and side-effects have been evaluated by psychometric tests. The EEG is a proven parameter with regard to dosage determination and as objective means to find sleep-inducing quantities of drugs. By means of vigilosomnograms we have established dose-effect curves and have made comparisons between related drugs in the form of equivalence studies. From an anaesthesiological point of view controllability of a substance is determined by duration of effect (short- or long-acting) and by depth of sleep (light or deep states) achieved. By these criteria midazolam displays good controllability with regard to duration, but not in terms of depth of sleep, since it follows the \"all-or-nothing\" rule, even with 0.1 mg/kg following both intravenous or intramuscular injection. Lormetazepam, on the other hand, shows good controllability of depth of sleep from tranquillity via sedation to hypnosis, but duration of effect is less well controllable in that patients remain lightly asleep even after 2 h. According to the vigilosomnograms the lormetazepam/oxygen/nitrous oxide combination produced a super-added increase in the depth of the hypnotic effect. After droperidol the specific nitrous oxide component of the depth of sleep at Bo stage was not exceeded. The development of benzodiazepine antagonists, which immediately counteract the benzodiazepine induced sleep and respiratory obstruction is a milestone in the area of CNS research.</p>","PeriodicalId":77887,"journal":{"name":"Psychopharmacology. Supplementum","volume":"1 ","pages":"119-32"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17442286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are poor sleepers changed into good sleepers by hypnotic drugs?","authors":"K Adam","doi":"10.1007/978-3-642-69659-6_3","DOIUrl":"https://doi.org/10.1007/978-3-642-69659-6_3","url":null,"abstract":"<p><p>Sleep can be measured by subjective ratings, electrophysiological recordings and by the physiological and biochemical changes occurring with sleep. Using these methods, we can select those who rate their sleep as unsatisfactory and those who feel fully satisfied by their sleep. Electrophysiological recordings of sleep show that there are relatively small differences between these good and poor sleepers: poor sleepers sleep less than good sleepers, but not as little as they think. However, the complaints of poor sleepers that they feel unrestored by their sleep should not be dismissed, for investigations employing the tools of physiology and biochemistry have revealed differences between good and poor sleepers that suggest that the sleep of poor sleepers may indeed be less restorative. The actions of hypnotic drugs on sleep can be similarly investigated. Preliminary findings suggest that hypnotic drugs may reverse some of the detrimental metabolic concomitants of poor sleep.</p>","PeriodicalId":77887,"journal":{"name":"Psychopharmacology. Supplementum","volume":"1 ","pages":"44-55"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17441254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Are the amplitudes of visual evoked potentials sensitive indices of hangover effects after repeated doses of benzodiazepines?","authors":"J J Kulikowski,&nbsp;F F McGlone,&nbsp;K Kranda,&nbsp;H Ott","doi":"10.1007/978-3-642-69659-6_13","DOIUrl":"https://doi.org/10.1007/978-3-642-69659-6_13","url":null,"abstract":"<p><p>Here we compared the efficacy of two electrophysiological techniques in detecting hangover effects after repeated administration (five days) of benzodiazepines. Twelve hours after the last ingestion, possible effects on evoked potentials (EPs) of the long- and short-acting benzodiazepines, flurazepam and lormetazepam, were compared here with those of placebo under a double-blind experimental condition. The EPs were recorded from occipital and parietal sites during an active discrimination of two amoeboid shapes and passive viewing of sine-wave grating patterns turned on and off. In the former task, the subject was requested to make a selective response with respect to whether the two shapes appeared the same or different and his reaction times were simultaneously recorded. Neither benzodiazepine influenced the latencies of any of the sensory and late EP components. Flurazepam's long-acting metabolite, N-desalkylflurazepam, reduced the amplitudes of all the EP components suggesting a somewhat general mode of action. This was not the case for lormetazepam. N-desalkylflurazepam reduced the amplitudes of the occipital visual evoked potentials (VEPs) to sine-wave gratings to a greater extent than the amplitudes of the late parietal EPs to amoeboid shapes. This effect did not show any particular preference for either of the subsystems processing pattern and movement information. The amplitudes of the late EP components, such as N200 and P300 waves recorded from parietal sites, were reduced considerably more after flurazepam administration than their counterparts recorded from the occiput. This observation points to the possible existence of at least two separate sources of the N200-P300 complex with different affinities to the N-desalkylflurazepam. The flurazepam-induced amplitude reduction observed for VEPs to gratings may reflect an attenuation in the detectability of both pattern and movement. The attenuation of the late EP amplitudes is possibly a function of several processes, one of which is conceivably the anxiolytic property of flurazepam which lowers the level of the activation state and this in turn is known to contribute to the amplitude size of the N200-P300 complex.</p>","PeriodicalId":77887,"journal":{"name":"Psychopharmacology. Supplementum","volume":"1 ","pages":"154-64"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17213209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amnesic effects of lormetazepam.","authors":"T Roehrs,&nbsp;A McLenaghan,&nbsp;G Koshorek,&nbsp;F Zorick,&nbsp;T Roth","doi":"10.1007/978-3-642-69659-6_14","DOIUrl":"https://doi.org/10.1007/978-3-642-69659-6_14","url":null,"abstract":"<p><p>Sixteen healthy men, age 18-35, each received lormetazepam (1.5 mg), flurazepam (30 mg), temazepam (30 mg) and placebo (double-blind in a Latin Square design) 30 min before bedtime for 2 consecutive nights followed by a 12 day washout between conditions. Three hours after drug (2.5 h after bedtime) subjects were awakened and administered a 16-item memory task. Fifteen minutes after the awakening subjects returned to bed, were instructed to go to sleep, and remained in bed for an additional 5.5 h. Immediately after the memory tasks, before returning to bed, subjects recalled almost all of the 16 items when placebo was administered before bedtime. Immediate recall was significantly poorer than placebo after temazepam and flurazepam, but not after lormetazepam. Morning recall was reduced significantly from the immediate nighttime level in each condition; this loss was smallest with placebo. All active drug conditions produced significantly greater amnesia than placebo. This amnesia was smallest after lormetazepam and greatest after temazepam, which differed significantly from each other. All active drugs significantly reduced latency measures of the return to sleep after the 15 min awakening; it was shortest with temazepam and longest with flurazepam. This study showed a relation between the hypnotic and amnesic effects of these drugs which is consistent with their pharmacokinetic properties.</p>","PeriodicalId":77887,"journal":{"name":"Psychopharmacology. Supplementum","volume":"1 ","pages":"165-72"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17213211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypnotic drugs for 1984.","authors":"I Oswald","doi":"10.1007/978-3-642-69659-6_7","DOIUrl":"https://doi.org/10.1007/978-3-642-69659-6_7","url":null,"abstract":"<p><p>It is still insufficiently recognised that hypnotics and anti-anxiety drugs are one and the same and that the regular intake of these drugs will be followed by withdrawal phenomena, including complaints of insomnia and anxiety. The long-acting, cumulative drugs like phenobarbitone or flurazepam cannot in reality be withdrawn abruptly owing to their persistence in the tissues, and so they do not cause sharp rebound phenomena, though they cause impaired skills and judgement by day. Very short life drugs, like triazolam, are followed by immediate and severe withdrawal insomnia in older people and their regular nighttime intake may cause regular daytime withdrawal symptoms of enhanced anxiety. A hypnotic with a half-life of about 10 hours may be the most sensible compromise to provide sleep by night without serious positive or negative daytime effects, though some eventual withdrawal features will be inevitable. The benzodiazepines lead to a degree of tolerance, but this is never complete and their positive effects are sustained over many months. Increased sleep duration has been assumed to be a necessary feature of an effective hypnotic. However, hypnotic drugs for the future might not lengthen sleep, but improve it's restorative value and the subjective satisfaction given to the patient.</p>","PeriodicalId":77887,"journal":{"name":"Psychopharmacology. Supplementum","volume":"1 ","pages":"84-90"},"PeriodicalIF":0.0,"publicationDate":"1984-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17213954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}