Biomedical subjects
A N Nicholson
Publications and source records attributed to A N Nicholson.
Response to transient haemorrhage after acute and chronic section of the carotid sinus nerves.
Adaptation to denervation of the carotid sinus region was studied on cats during hypotension induced by a controlled haemorrhage. After denervation, the fall in arterial pressure in response to haemorrhage was increased, but rhe partial recovery of blood pressure was preserved. In chronic animals, this pattern of response was also seen, but a resting hypertension developed and ensured that the minimal blood pressure and the recovery reached during the haemorrhage were similar to those of intact animals. The studies suggest that the primary role of the carotid receptors is to minimize the effect of stresses which lead to hypotension, rather than to set the level of the resting blood pressure.
Comparative studies with thieno- and benzodiazepines: spatial delayed alternation behaviour in the monkey (Macaca mulatta).
Explore the source record for details and available documents.
A synthetic ACTH4-9 analogue )Organon 2766) and sleep in healthy man.
Explore the source record for details and available documents.
Studies on sleep and performance with a triazolo-1, 4-thienodiazepine (brotizolam).
1 Brotizolam, a triazolo-1,4-thienodiazepine, was studied in healthy young adults. Electroencephalographic sleep variables and subjective effects, and performance on a visuo-motor coordination task were measured. 2 In the sleep studies six males each ingested 0.2, 0.4 and 0.6 mg brotizolam overnight. 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 and increased stage 2 sleep. 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. 3. In the performance studies six females each ingested 0.4 mg in the morning and 0.2, 0.4 and 0.6 mg brotizolam at night. After morning ingestion of 0.4 mg there was impaired performance from 0.5 to 5.5 h. There were no residual effects after 0.2 mg brotizolam, but with 0.4 mg there was a residual effect at 9.5 h, and 0.6 mg led to impairments up to 15.0 h after ingestion. 4 Brotizolam is a short-acting hypnotic. In doses around 0.2 mg it has useful hypnotic activity free of adverse effects on sleep and residual effects on performance. With 0.4 mg the hypnotic effect is enhanced with only minimal residual effects.
Efficacy of some benzodiazepines for day-time sleep.
1 Effects of flunitrazepam (0.25-0.50 mg) and the 1,4-triazolodiazepines, triazolam (0.25-0.50 mg) and brotizolam (0.3-0.6 mg), on day time sleep were studied by electroencephalography. 2 Flunitrazepam (0.25-0.50 mg) and triazolam (0.25-0.50 mg) reduced awake activity (P < 0.05) and improved the sleep efficiency index (P < 0.05). The higher dose of each drug increased total sleep time (P < 0.05 and < 0.01 respectively) and duration of stage 2 sleep (P < 0.01), and also delayed the first REM period (P < 0.05 and < 0.01 respectively). 3 Brotizolam (0.6 mg) markedly increased total sleep time (P < 0.001) and the sleep efficiency index (P < 0.01), and prolonged stages 2 (P < 0.01 and slow wave (P < 0.01) sleep. Over the dose range 0.3-0.6 mg, the latency to stage 3 sleep was shortened (P < 0.05), and that to the first REM period lengthened (P < 0.05). 4 All three drugs improved day time sleep. However the present observations and data from previous studies suggest that flunitrazepam (0.25-0.50 mg) may be particularly appropriate for sleep at unusual times.
Wakefullness and reduced rapid eye movement sleep: studies with prolintane and pemoline.
1 Effects of prolintane (15 and 30 mg) and pemoline (60 and 100 mg) on sleep were studied in six healthy adult males. Sleep was assessed by electroencephalography and by analogue scales. 2 Prolintane (15 and 30 mg) reduced rapid eye movement (REM) sleep both by delaying the first period (P < 0.05 and < 0.001 respectively) and by reducing total REM sleep (P < 0.05 and < 0.001 respectively). In some subjects there were increased awakenings during the early part of the night, and in two subjects long periods of wakefulness occurred. 3 With pemoline (60 and 100 mg) sleep duration was marked reduced (P < 0.001). There was evidence in some subjects of delay to the first REM period, and reduced percentage REM sleep (P < 0.01). Shortened and fragmented sleep with 60 and 100 mg were associated with reduced sleep efficiency indices (P < 0.001), and shorter sleep period times led to reduced REM/NREM ratios. Absence of an effect on REM latency for the subjects as a group may be related to relatively slow absorption. 4 The heterocyclic amphetamine derivatives have variable effects on sleep. The differences may be dose related, and wakefulness and reduced REM sleep may be seen together or separately. Alterations in sleep occur with doses of pemoline and prolintane which also modify performance.
Hypnotics: rebound insomnia and residual sequelae.
Explore the source record for details and available documents.
Activity of the hypnotics, flunitrazepam and triazolam, in man.
Explore the source record for details and available documents.
Heterocyclic amphetamine derivatives and caffeine on sleep in man.
Explore the source record for details and available documents.
Beta-adrenoceptor antagonists: studies on behaviour (delayed differentiation) in the monkey (Macaca mulatta).
1 Activity of six beta-adrenoceptor antagonists was studied on behavioural activity (delayed differentiation) in the monkey (Macaca mulatta). The drugs, three relatively lipophilic antagonists (propranolol, oxprenolol and metoprolol), and three relatively hydrophilic antagonists (acebutolol, atenolol and sotalol), were given by intraperitoneal injection (5 to 30 mg/kg).2 With atenolol (25 to 30 mg/kg), total response time was increased, but there was no effect on the number of correct responses. With acebutolol (25 to 30 mg/kg), the number of correct responses was reduced, but there was no effect on total response time. With metoprolol (25 to 30 mg/kg), there was an increase in total response time and a decrease in the number of correct responses, and correct responses were decreased 4 h after injection over the whole dose range (5 to 30 mg/kg).3 Some animals failed to respond or complete the task with 30 mg/kg oxprenolol, 25 mg/kg sotalol and 20 mg/kg propranolol. With 25 mg/kg oxprenolol, the total response time was increased and the number of correct responses was decreased. With 5-20 mg/kg sotalol, total response time was increased, but there was no effect on the number of correct responses. With 15 mg/kg of (+/-)-propranolol and its isomers, there were increases in total response time and decreases in correct responses.4 The studies suggest that lipophilic antagonists, such as propranolol, oxprenolol and metoprolol, are likely to have, at least, effects on the central nervous system, while hydrophilic antagonists may modify the peripheral nervous system. In the dose-ranges studied, propranolol had the greatest, and atenolol and acebutolol had the least effects. Atenolol and acebutolol may prove to be particularly useful in man when disturbances of the nervous system are to be avoided.
L-tryptophan and sleep in healthy man.
The effect of L-tryptophan on night-time and day-time sleep (from 14.00 h) sleep was studied in six healthy males aged between 20 and 30 years. The doses used in the night-time studies were 2, 4 and 6 g, and in the day-time studies 1, 2 and 4 g. It was not possible to establish an effect of L-tryptophan compared with placebo on night-time sleep, but analysis of the sleep measures with 4 g compared with placebo and the other doses of L-tryptophan considered together suggested reduced awakenings, increased stage 3 and an increased percentage of REM sleep. With 4 g L-tryptophan there was an increase in the duration of stage 3 of day-time sleep compared with placebo. The studies provide marginal evidence that REM sleep may be modified by L-tryptophan in man, though the evidence is somewhat stronger that SWS may be increased. The effect on REM sleep may involve circadian mechanisms. The hypnotic activity of L-tryptophan per se is limited and uncertain.
Adverse central effects of drugs in man: predictive value of behavioral studies in rodents and primates.
Explore the source record for details and available documents.
Performance studies with diazepam and its hydroxylated metabolites.
1 Visuo-motor coordination has been used to study the immediate and residual effects of benzodiazepines on performance in man. The technique provides dose and time response data related to the decrement and the persistence of impaired performance. 2 With the overnight ingestion of flurazepam hydrochloride 30 mg and nitrazepam 10 mg, performance was impaired to 16 h and, at least, 19 h, respectively. Performance was not impaired after the overnight ingestion of diazepam, 5 and 10 mg, temazepam 10, 20 and 30 mg or oxazepam 15 and 30 mg. However, with temazepam 30 mg there was a trend toward impaired performance,, and with oxazepam 45 mg, performance was impaired 10 h after ingestion. With morning ingestion, coordination was impaired 0.5 and 2.5 h after diazepam 10 mg, at 0.5 h after temazepam 20 mg, and after oxazepam 30 mg at 2.5 and 4.5 hours. 3 The studies suggest that diazepam 5-10 mg, temazepam 10-20 mg and oxazepam 15-30 mg may be of use in the management of sleep disturbance when impaired performance the next day is to be avoided.
Diazepam and 3-hydroxydiazepam (temazepam) and sleep of middle age.
Explore the source record for details and available documents.
Differential effects of the 1,4 and 1,5 benzodiazepines on performance in healthy man.
1 The immediate and residual effects on performance of benzodiazepines differ, and the differences are important in the use of these drugs. 2. Diazepam and its hydroxylated metabolites, temazepam and oxazepam, each possess hypnotic activity, and have effects on performance limited to the sleep period. The demethylated metabolite of diazepam, nordiazepam, and its precursor, potassium clorazepate, which also possess hypnotic activity, have a longer duration of action, although the next day anxiolytic effect is accompanied by only minimal effects on performance. The 1.5 benzodiazepine, clobazam, seems to have minimal immediate effects on performance. 3 Diazepam and its hydroxylated metabolites, temazepam and oxazepam, would be useful in the management of insomnia without psychopathology in those cases in which residual effects on performance must be avoided. Nordiazepam and potassium clorazepate would be appropriate for insomnia secondary to day-time anxiety, and clobazam may be useful as a day-time anxiolytic. 4 It is emphasized that more work needs to be carried out on the effects of anxiolytics on performance before one can be certain that ingestion during the day would be without any deleterious effects on skilled work.
Effect of the antihistamines, brompheniramine maleate and triprolidine hydrochloride, on performance in man.
1 Effects of brompheniramine maleate (4 and 12 mg) and triprolidine hydrochloride (2.5 and 10 mg) on visuo-motor coordination, and on subjective assessments of performance, well-being and sleep were each studied in six subjects at 0.5, 1.5, 3.0, 5.0 and 7.0 h after ingestion. The doses refer to immediate and sustained release preparations respectively. 2. Triprolidine hydrochloride (2.5 mg) had an immediate effect on performance which persisted to 3.0 h, and the sustained release preparation (10 mg) impaired performance from 1.5 to 5.0 h. Brompheniramine maleate (4 mg) impaired performance from 1.5 to 3.0 h, and the sustained release preparation (12 mg) impaired performance at 1.5 h. There were no consistent changes in the subjective assessments of performance, or of well-being and sleep. 3. The studies emphasize the variable effects of antihistamines on performance, and suggest that effects on performance of sustained release preparations may be similar to those of the usual form. Sustained release preparations may provide an advantage in clinical practice if the antihistaminic activity is prolonged.