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Biomedical subjects

A N Nicholson

Publications and source records attributed to A N Nicholson.

At least 91 records · Page 5Linked to original sources
PubMed1983

Midazolam: sleep and performance studies in middle age.

Effects of 10, 20 and 30 mg midazolam on sleep and on performance the next day were studied in six healthy adult males aged between 47 and 53 years. The study was double-blind, placebo-controlled and included another rapidly eliminated benzodiazepine (brotizolam, 0.25 mg) as an active control. With 10 mg midazolam, sleep-onset latency was quicker, and the duration and percentage of stage 2 sleep was increased over the first 6 h. Effects of 20 and 30 mg midazolam were similar to each other. Sleep onsets were earlier, total sleep times and stage 2 sleep were increased, and the sleep efficiency indices improved. During the first 6 h there was reduced duration and percentage of drowsy (stage 1) sleep. There was no consistent evidence of delay to the first period of rapid eye movement sleep, but over the dose range the duration was reduced during the first 2 h. Digit symbol substitution did not show any residual decrement 9 h after ingestion of 10, 20 or 30 mg midazolam. Midazolam may prove to be a particularly useful hypnotic for shiftworkers whose rest periods tend to be shorter than in those who have a regular nocturnal sleep pattern.

Anti-Anxiety Agents↗
PubMed1983

Brotizolam: studies of effects on sleep and on performance in young adulthood and in middle age.

Effects of brotizolam (0.2, 0.4 and 0.6 mg), on sleep and performance, were studied in young adults. All doses increased total sleep time, improved the sleep efficiency index, and reduced drowsy sleep and number of awakenings. Brotizolam (0.4 and 0.6 mg) also reduced awake activity. There was some evidence of a delay to the first REM period, but only 0.6 mg reduced the total duration of REM sleep. There were no changes in slow wave sleep. Visuomotor coordination was impaired up to 15.0 h after overnight ingestion of 0.6 mg, but there were no residual effects after the overnight ingestion of 0.2 mg, and with 0.4 mg residual effects did not persist beyond 9.5 h. In middle-aged subjects 0.25 and 0.5 mg were studied. The lower dose (0.25 mg) increased total sleep time, and improved the sleep efficiency index, shortened sleep onset latency, and reduced drowsy sleep. The effect of the higher dose (0.5 mg) was more marked. In a performance study using digit symbol substitution, no residual effect was observed after 0.25 mg brotizolam. Brotizolam is a short-acting hypnotic. Doses up to 0.25 mg are likely to prove adequate over the main span of life and be free of adverse effects on sleep and residual effects on performance.

Adult↗
PubMed1983

Zopiclone: sleep and performance studies in healthy man.

Effects of 2.5, 5.0, 7.5, and 10.0 mg zopiclone on sleep and on performance the next day were studied in 6 healthy adult males aged between 21 and 33 years. The experiment was double-blind and placebo controlled. 5.0 and 10.0 mg zopiclone decreased the amount of awake activity and drowsy (stage 1) sleep over the first 6 h of sleep, but this effect was only present for the whole sleep period with the 10.0-mg dose. The duration and percentage of stage 3 sleep were increased with 7.5 mg. The 7.5- and 10.0-mg doses increased the combined duration of stages 2, 3, and 4 sleep over the first 6 h and over the whole night. The first period of rapid eye movement sleep was delayed with 7.5 mg, and with 10.0 mg the time spent in rapid eye movement sleep was reduced during the first 6 h of sleep, but not over the whole night. The number of substitutions in the digit symbol substitution test was decreased 9 h after ingestion of 7.5 and 10.0 mg, and the number of symbols copied reduced after 10.0 mg. The clinical dose range of zopiclone is likely to be up to 7.5 mg. The latter dose provides a useful hypnotic effect with minimal residual effects the next day, whilst 5.0 mg is appropriate for those involved in skilled tasks where even the most minor changes in performance during the early part of the next day must be avoided.

Adult↗
PubMed1983

Persistence of the effects of benzodiazepines. Pharmacodynamic studies in man.

The dynamic correlates of the pharmacokinetic profiles of various benzodiazepines used as hypnotics are described using impairment of performance. In particular, rate of absorption and the nature of the distribution phase are discussed, and the way in which the pharmacokinetic profile relates to clinical use.

Anti-Anxiety Agents↗
PubMed1983

Imidazobenzodiazepines: sleep and performance studies in humans.

For hypnotics in which a fast elimination phase dominates the plasma decay, the initial fall in concentration from the peak value may nevertheless be slower than that of compounds with a sustained and rapid distribution. Drugs with fast elimination may therefore improve sleep throughout the rest period, even though residual sequelae, if any, around awakening will disappear rapidly. In the context of the balance between efficacy and residual effects, the activity of two imidazobenzodiazepines, loprazolam (0.5, 1.0, and 1.5 mg) and midazolam (10, 20, and 30 mg), each with fast elimination (about 6 and 2 hours, respectively) has been studied in healthy men with sleep electroencephalography, measures of performance, and assessments of mood. Loprazolam may be appropriate when a sustained hypnotic effect is required and when some residual activity is acceptable, while midazolam is likely to be suitable for those involved in skilled activity and may be useful in the management of sleep disturbance associated with shift work.

Adolescent↗
PubMed1982

6-(3-chloro)-phenoxy-2-methyl-1-oxa-4-azospiro-[4,5]decane-3-one (CERM 3726) and sleep of healthy men.

Immediate effects on sleep of 100, 200 and 300 mg 6-(3-chloro)-phenoxy-2-methyl-1-oxa-4-azospiro-[4,5]decane-3-one (CERM 3726) were studied in six healthy males. There was some sleep disturbance in two subjects with 100 and 200 mg, but only with 300 mg was there unequivocal evidence of reduced total sleep time and stage 2 sleep, together with a trend toward reduced rapid eye movement sleep. Arousal, at least as indicated by sleep studies, may be associated with the reported effect of the drug to oppose the deterioration in performance of tests of prolonged duration.

Adult↗
PubMed1982

Performance studies with the H1-histamine receptor antagonists, astemizole and terfenadine.

1 Effects of the antihistamines, terfenadine (60 mg) and astemizole (10 and 20 mg), on performance (visuo-motor coordination, arithmetical ability and digit symbol substitution) and on mood were studied in six healthy adult females. The study was double-blind, placebo controlled and included an antihistamine with known central effects (triprolidine 10 mg in sustained release form). 2 There were no changes in performance after terfenadine (60 mg) and astemizole (10 and 20 mg). Triprolidine (10 mg) caused a decrement in visuo-motor coordination (P less than 0.01) 0.5 h after ingestion which lasted until 3.5 h (P less than 0.001). The subject assessed their performance as impaired from 1.5-3.5 h (P less than 0.05) with triprolidine (10 mg), and their mood assessments were also altered. 3 Terfenadine (60 mg) and astemizole (10 and 20 mg) are likely to prove useful antihistamines for those involved in skilled activity.

Adult↗
PubMed1982

Hypnotic activity and effects on performance of lormetazepam and camazepam--analogues of temazepam.

1 The effects of lormetazepam and camazepam on sleep electroencephalography, visuo-motor coordination, digit symbol substitution and subjective assessments of mood and sleep quality were compared with placebo in six young adult males (18-27 years). The study was double blind. 2 Over the dose range 0.5, 1.0 and 2.0 mg, lormetazepam increased total sleep time (P less than 0.05), reduced wakefulness (P less than 0.05) and drowsy sleep (linear effect P less than 0.05). With 2.0 mg there were increases in stage 3 (P less than 0.05) and reduction in rapid eye movement sleep (P less than 0.01). Overnight ingestion of 2.0 mg, was followed by impaired visuo-motor coordination and fewer substitutions with the digit symbol test. 3 The hypnotic effect of 10-20 mg camazepam was limited to reduced awake activity (P less than 0.05), and with 20 mg there were increased substitutions on the digit symbol test. After 40 mg overnight stage 4 sleep was reduced (P less than 0.001) and performance at the digit symbol test was impaired (P less than 0.05 at 9.75 h). Morning ingestion of 20 mg camazepam did not alter performance, and the subjects assessed themselves to be more relaxed. 4 Lormetazepam is not specially indicated for those involved in skilled activity, but may prove useful for patients with insomnia resistant to other drugs. Camazepam would appear to be a promising anxiolytic with minimal effects on performance.

Adolescent↗
PubMed1982

Antihistamines and visual function: studies on dynamic acuity and the pupillary response to light.

1 Effects of three antihistamines, triprolidine (10 mg) in a sustained release form, astemizole (10 mg) and terfenadine (60 mg), have been studied on dynamic visual acuity and on the response of the pupil to light, together with critical flicker fusion, digit symbol substitution and cancellation, and subjective assessment of mood. The study was double-blind and effects were observed from 0.5-4.0 h after ingestion. 2 Triprolidine impaired dynamic acuity and reduced the threshold for subjective fusion of a flickering light, but there were no changes with astemizole or terfenadine. The diameter of the pupil and its response to light were not changed by the drugs. 3 Performance on digit symbol substitution and cancellation was not altered by the drugs. 4 Astemizole and terfenadine are promising antihistamines for those involved in skilled activity.

Adult↗
PubMed1982

[Anxiolytics in man: studies on sleep and performance (author's transl)].

The development of the benzodiazepin molecule has led to drugs which are specially indicated in the management of anxiety. Such drugs may be ingested overnight in which a beneficial effect on sleep is followed by an anxiolytic effect the next day, or during the day. In each case it is desirable that their day time effect is without or with only minimal impairment of performance. In the present paper studies on the effects of two anxiolytic (potassium chlorazepate and clobazam) on sleep and on performance will be reviewed. Potassium chlorazepate is usually given as a single dose (15 mg) overnight. It has useful hypnotic activity and a sustained anxiolytic effect the next day related to the activity of its long-acting metabolite, nordiazepam. Further, unlike most if not all other, 1,4 benzodiazepines it is difficult to unequivocally impairment of performance. On the other hand clobazam is usually given as repeated doses (10-20 mg) during the day, and with this 1,5-benzodiazepine it is also difficult to establish impairments of performance. Anxiolytics without impairment of performance during the day have obvious clinical advantages, and if they also have a useful hypnotic activity they can be particularly appropriate for the management of insomnia secondary to anxiety.

Anti-Anxiety Agents↗
PubMed1982

Zopiclone: sleep and performance studies in healthy man.

Effects of 2.5, 5.0, 7.5, and 10.0 mg zopiclone on sleep and on performance the next day were studied in 6 healthy adult males aged between 21 and 33 years. The experiment was double-blind and placebo controlled. 5.0 and 10.0 mg zopiclone decreased the amount of awake activity and drowsy (stage 1) sleep over the first 6 h of sleep, but this effect was only present for the whole sleep period with the 10.0-mg dose. The duration and percentage of stage 3 sleep were increased with 7.5 mg. The 7.5- and 10.0-mg doses increased the combined duration of stages 2, 3, and 4 sleep over the first 6 h and over the whole night. The first period of rapid eye movement sleep was delayed with 7.5 mg, and with 10.0 mg the time spent in rapid eye movement sleep was reduced during the first 6 h of sleep, but not over the whole night. The number of substitutions in the digit symbol substitution test was decreased 9 h after ingestion of 7.5 and 10.0 mg, and the number of symbols copied reduced after 10.0 mg. The clinical dose range of zopiclone is likely to be up to 7.5 mg. The latter dose provides a useful hypnotic effect with minimal residual effects the next day, whilst 5.0 mg is appropriate for those involved in skilled tasks where even the most minor changes in performance during the early part of the next day must be avoided.

Adult↗
PubMed1981

The use of short- and long-acting hypnotics in clinical medicine.

1 Activity of short- and long-acting benzodiazepines is reviewed with reference to pharmacokinetics and residual sequelae, and to efficacy and adverse effects. 2 Some benzodiazepines may not lead to obvious effects on performance, such as nordiazepam and clobazam, and the persistence of residual sequelae may not relate obviously to elimination half-lives (as with diazepam and possibly flunitrazepam). However, benzodiazepines with mean half-lives less than 8 h may have residual sequelae, whereas hypnotics with mean half-lives greater than 16 h are likely to lead to impared performance and/or anxiolytic effects the next day. 3 Potassium chlorazepate 15 mg, with its long-acting metabolite nordiazepam, would seem to be the drug of choice for insomnia secondary to anxiety. For the insomniac without significant psychopathology, temazepam 10-20 mg, triazolam 0.125-0.25 mg and for occasional use, diazepam 5-10 mg, provide the initial approach. Flurazepam hydrochloride 15-30 mg, nitrazepam 5-10 mg and flunitrazepam 1 mg and above, have persistent residual effects and should be reserved for refractory patients, and for those in whom some impairment of performance the next day would be acceptable. 4 There is little or no evidence to suggest that the proper use of the short-acting hypnotics, triazolam and temazepam, leads to a worsening of sleep on withdrawal. However, some benzodiazepines may lead to disturbances of sleep and/or rebound insomnia, and nitrazepam and flunitrazepam may be implicated.

Anti-Anxiety Agents↗