1 The effects of 10mg (+)-and (-)-chlorpheniramine and 5mg (+)-and (-)-dimethindene on daytime sleep latencies, digit symbol substitution and subjective assessments of mood and well-being were studied in 6 healthy young adult humans. Each subject also took 5mg triprolidine hydrochloride as an active control and two placebos. 2 Daytime sleep latencies were reduced with triprolidine, (+)-chlorpheniramine and (-)-dimethindene, and subjects also reported that they felt more sleepy after (+)-chlorpheniramine and (-)-dimethindene. Performance on digit symbol substitution was impaired with (+ )-chlorpheniramine. 3 Changes in measures with (-)-chlorpheniramine and (+)-dimethindene were not different from changes with placebo. 4 In the present study, changes in measures of drowsiness and performance were limited to the enantiomers with high affinity for the histamine Hl-receptor. These findings strongly suggest that sedation can arise from H1-receptor antagonism alone, and provide further support for the belief that the histaminergic system is concerned with the regulation of alertness in man.

1 The residual effects of two benzodiazepines, nitrazepam (10 mg) and flurazepam hydrochloride (30 mg), and pentobarbitone sodium (200 mg) were studied by adaptive tracking and by reaction time. Performance was measured at 10 h, 13 h, 16 h, 19 h and 34 h after ingestion of each drug. Impaired performance on adaptive tracking was observed at 10 h, 13 h, 16 h and 19 h after nitrazepam and pentobarbitone sodium and at 10 h, 13 h and 16 h after flurazepam hydrochloride. Enhanced performance was observed at 34 h after nitrazepam and pentobarbitone sodium. 2 Increased reaction time persisted to 16 h after nitrazepam, flurazepam hydrochloride and pentobarbitone sodium and reaction time was also increased at 34 h after nitrazepam and pentobarbitone sodium. 3 During the morning immediately after ingestion, the subjects as a group were able to differentiate correctly between placebo and drugs, but they were not able to assess accurately the persistence of the residual effects of nitrazepam and pentobarbitone sodium. 4 Flurazepam hydrochloride would appear to be a more promising benzodiazepine than nitrazepam for use as a hypnotic by persons involved in skilled activity. There was a rapid recovery of performance during the afternoon and, unlike pentobarbitone sodium and nitrazepam, subjects retained the ability to recognize impaired skill.

1 Effects of the heterocyclic amphetamine derivatives, pemoline (20 and 40 mg), prolintane hydrochloride (5 and 10 mg), methylphenidate hydrochloride (10 and 20 mg) and fencamfamine hydrochloride (10 and 20 mg), and of caffeine anhydrous (100, 200 and 300 mg) on sleep, were compared with placebo in six young adults (20-31 years) using electroencephalography for sleep measures and analogue scales for subjective assessments of well-being and sleep quality. The

Data on the effect of an antihistamine (triprolidine 10 mg) on visuo‐ motor coordination and dynamic visual acuity were used to establish interactions between these skills. Analysis of covariance and principal component analysis were used. The analyses suggested two main effects‐ an effect on the activity of the neuromuscular system and one which impaired ability to anticipate target movement. Detection of impaired performance by any task may have wider implications to the effectiveness of the individual than that obviously suggested by the skill itself.

1 Central effects of the P-adrenoceptor antagonists, propranolol (40, 80 and 160 mg) and atenolol (50 and 100 mg) were studied in 12 healthy male subjects. Two placebo ingestions and an active control (oxazepam 15 mg) were included. Single doses were administered double-blind at 11.00 h, and assessments of performance and subjective feelings were made before, 2 h and 4 h after ingestion. 2 Performance was measured using letter cancellation, digit symbol substitution, continuous attention, choice reaction time, finger tapping, short term and immediate memory, critical flicker fusion and two flash fusion. Subjective feelings were assessed using twelve visual-analogue scales.3 Oxazepam impaired performance at letter cancellation (P < 0.001), digit symbol substitution (P < 0.05), continuous attention (P < 0.001), immediate recall (P < 0.05) and finger tapping (P < 0.05), but neither of the 3-adrenoceptor antagonists affected these measures. Propranolol (40 and 160 mg) also impaired short term memory (P < 0.05), though it was not possible to establish this effect with atenolol.4 Subjective alertness was reduced by oxazepam (P < 0.01) and atenolol (P < 0.05), while propranolol (40 mg) reduced anxiety (P < 0.01) and propranolol (80 mg) impaired ability to concentrate (P < 0.05). 5 The results suggest that both lipophilic and hydrophilic antagonists modify the central nervous system, though impairment may be difficult to establish with conventional tests.The observations on memory and alertness suggest that the central effect of P-adrenoceptor antagonists may be subtle. Keywords ,B-adrenoceptor antagonists propranolol atenolol performance IntroductionThere is uncertainty concerning the nature of the Fleming, 1978). However, presently available possible central effects of 1-adrenoceptor an-information is difficult to evaluate. Impaired tagonists, but, though it is likely that these drugs performance has been reported after single doses have such effects, their severity may be minimal (Bryan et al., 1974;Glaister et al., 1973; Landauer compared with the benzodiazepines. Indeed, et al., 1979;Salem & McDevitt, 1983), while light-headedness, visual and auditory halluci-other studies have failed to show such effects nations, sleep disturbances, vivid dreams and (Ogle etal., 1976;Turner & Hedges, 1973 In this paper we report the observations on various aspects of performance as well as subjective assessments of well being and mood, and in the following paper we deal with the findings on the electroencephalogram and body sway. Methods Experimental designTwelve healthy male volunteers, aged between 19 and 29 years, participated in the study which was approved by the Hospital Ethics Committee. None was taking any concurrent medication and each was required to abstain from alcohol for 24 h before each study period. No caffeinecontaining beverages were permitted during the study days.Performance was tested in individual, soundproofed cubicles. The intensity of lighting could be adjusted to permit dark adaptation before measurem...

INTRODUCTION THERE IS MUCH INTEREST CONCERNING THEACTIVITY OF MELATONIN and how melatonin may be used to alleviate disturbances of circadian rhythmicity and insomnia. Experimental work on the possible adjustment of the circadian clock by melatonin is complicated by its sedative activity. This latter effect may improve sleep, thus alleviating the symptomatology of circadian desynchrony, and even normalizing the sleep-wake cycle. Whether melatonin can induce a phase shift of circadian rhythms is an issue much debated. 1,2,3 It may elicit a relatively weak phase shifting effect, but Cziesler 4 has emphasised that this may be insufficient to induce a reliable entrainment. Any such effect with melatonin needs to be established by physiological parameters other than sleep and wakefulness.Although sedative activity of melatonin has been demonstrated, its usefulness as a hypnotic is not clear. Indeed, Roth and Richardson 5 have emphasized that the majority of studies have evaluated only a single dose, or a limited dose range, and that there is a need for unambiguous information on its activity related to dose and to time of administration. Further, dose response data using electroencephalography are essential to an adequate understanding of its activity. Daytime ingestion of melatonin would appear to lead to reductions in sleep latencies, 6,7,8,9 but studies on its activity around the normal time of sleep have failed to establish a useful clinical effect, except possibly in elderly insomniacs. 10,11,12 However, the usefulness of a hypnotic in the management of sleep disturbance associated with shiftwork or with world wide travel would be dependent on it being effective at all times of the circadian cycle, and it is in this context that we have carried out a dose response study on the activity of melatonin when given in the early and late evening in healthy volunteers. The activity of melatonin was studied on nocturnal sleep (23:00-07:30) and on evening sleep (18:00-24:00), using electroencephalography, and was compared with that of a benzodiazepine (temazepam 20 mg) which is often used by individuals coping with irregular patterns of rest in critical situations. METHODS SubjectsThe subjects were healthy male volunteers free of the use of medication. They gave informed consent to take part

1 Effects of an imidazo-pyridine (zolpidem: 10, 20 and 30 mg) on overnight sleep and on performance the next day were studied in young adults and in middle aged individuals. The young adults were used particularly as an homogenous group to establish any possible adverse effects of the drug on sleep and on performance the next day, and the middle aged subjects with their less restful sleep were used to study efficacy. 2 In the young adults zolpidem led to a marked increase in slow wave sleep with a reduction in stage 2 sleep. There were no significant changes in REM sleep, though there was a tendency for REM sleep to be delayed. 3 In the middle aged there was a reduction in awake activity and drowsy sleep with an increase in stage 2 sleep. The latency to REM sleep was increased but the duration of REM sleep over the whole night was not reduced. 4 Digit symbol substitution and a complex reaction time task were used to study performance, but there were no residual effects with zolpidem (9 h after ingestion). 5 Zolpidem is likely to prove useful in the management of transient and short-term insomnia in healthy middle aged individuals when impaired performance the next day is to be avoided.

1 Effects of the antihistamines, terfenadine (60 mg) and astemizole (10 and 20 mg), on performance (visuo-motor coordination, arithmetical ability and digit symbol substitition) 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 < 0.01) 0.5 h after ingestion which lasted until 3.5 h (P < 0.001). The subjects assessed their performance as impaired from 1.5-3.5 h (P < 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.