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Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance.

Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. However, it is not known whether this antagonistic effect of caffeine is mediated by a reduction in sleepiness. The present study assessed physiological alertness/sleepiness, memory, and psychomotor performance following the administration of placebo, ethanol, and caffeine+ethanol combinations. A total of 13 healthy individuals (21-35 years old) underwent four conditions presented in a Latin Square Design: placebo-placebo, ethanol (0.5 g/kg)-placebo, ethanol (0.5 g/kg)-caffeine 150 mg, and ethanol (0.5 g/kg)-caffeine 300-mg. The Multiple Sleep Latency Test (MSLT), psychomotor performance battery, memory test, and mood/sleepiness questionnaires were administered following each condition. The peak breadth ethanol concentration (BrEC) was 0.043+/-0.0197% and did not differ among the three caffeine treatments. As expected, ethanol reduced mean latency on the MSLT. The lowest caffeine dose reversed this effect and the highest dose increased mean latency (greater alertness) significantly beyond placebo levels. Ethanol also impaired psychomotor performance and memory. The 300-mg caffeine dose restored performance and memory measures to placebo levels. Although visual analog ratings of dizziness were increased by ethanol, they were not diminished by either caffeine dose. In conclusion, Low-dose caffeine prevented the sleepiness and performance impairment associated with a moderate dose of ethanol. Thus, caffeine, similar to other stimulants, can reverse the physiologically sedating effects of ethanol, although other negative effects remain.

Adult↗

Fluvastatin alters psychomotor performance and daily activity but not the spatial memory in rats.

Statins, inhibitors of cholesterol synthesis for treating dyslipidemia and preventing cardiovascular complications, have been shown to alter central nervous system functions. Our aim was to investigate the effects of the fluvastatin, a member of statin family, on psychomotor performance, daily activity and spatial memory. Sprague-Dawley rats were treated with fluvastatin (n = 8) or placebo as a control (n = 11) regardless of sex. Fluvastatin (7.5 mg/kg) was administered orally once a day for four weeks, while the control group was administered only placebo. Psychomotor performance was measured by rotarod tests. No significant difference was observed in the fluvastatin group over the course of weeks, but the control group preferred to stay on the device shorter times (p < 0.05). For the first three weeks of the drug administration there was a statistical difference between the groups, however no difference was found after the 4th week. There was no difference in the Barnes maze spatial memory test between the groups and also within the groups over the course of time. Daily activity tests revealed that stereotypical and vertical movements of the fluvastatin group were significantly less than the control group in all four weeks. Ambulatory movements and the distances taken by the fluvastatin group were decreased significantly over the course of time (p < 0.005 and p < 0.001, respectively), but the control group did not reveal any significant change. Our results suggest that fluvastatin altered psychomotor performance and daily activity in rats, but it did not affect the spatial memory. These behavioral changes might be associated with alterations in the composition of the brain lipids caused by fluvastatin.

Animals↗

Improved psychomotor performance in aged mice fed diet high in antioxidants is associated with reduced ex vivo brain interleukin-6 production.

Psychomotor performance is decreased in the aged. This study investigated the relationship between brain oxidative stress, interleukin-6 (IL-6) production by brain tissue ex vivo and psychomotor deficits during aging, and the effects of feeding an antioxidant-rich diet on ex vivo brain IL-6 production and motor function in aged mice. Male BALBc mice reared in SPF conditions and ranging in age from 3 to 24 months were studied. There was a precipitous decline in motor function after 12 months of age and an increase in brain lipid peroxidation and IL-6 production by coronal brain slices ex vivo. In another study, 12-month-old mice were fed diets formulated to provide a disparate range of antioxidants. At 18 months of age psychomotor coordination, motor learning, and ex vivo brain IL-6 production were evaluated. Mice fed an antioxidant-rich diet had improved psychomotor coordination compared to mice fed diet adequate or low in antioxidants. When mice were tested on successive days, only those fed adequate and high antioxidants exhibited motor learning. Analysis of IL-6 production by coronal brain slices indicated that as dietary antioxidants increased, IL-6 production decreased. Collectively, these data indicate that antioxidants improve psychomotor performance in aged mice, and suggest antioxidants may be useful for reducing brain IL-6 production, which has been shown to increase in aged mice.

Aging↗

Antidepressants, alcohol and psychomotor performance.

The acute psychomotor effects of moclobemide, a reversible inhibitor of MAO-A antidepressant (100 and 300 mg) compared with amitriptyline (25 and 75 mg) showed that moclobemide caused no significant impairment in contrast with amitriptyline, which caused significant impairment at both doses. Two other studies are reviewed. One study reported the acute effects of moclobemide (100 and 300 mg), trazodone (100 mg), placebo, and alcohol (0.5 g/kg) or placebo in an elderly group: moclobemide caused little impairment or alcohol potentiation and may reverse some alcohol impairment, whereas trazodone caused substantial impairment and alcohol potentiation. Another study of the acute and chronic effects of moclobemide (200 mg 3 times daily) or clomipramine (25 mg twice daily) and their interactions with alcohol (blood alcohol concentration 0.6 g/l) showed that alcohol caused significant impairment, whereas clomipramine tended to enhance and moclobemide to reduce some impairment. Moclobemide appears to be an antidepressant with few psychomotor effects and minimal alcohol potentiation and may reduce some alcohol impairment.

Antidepressive Agents↗

Computerised psychomotor performance testing: a comparative study of the single dose pharmacodynamics of minaprine and amitriptyline in young and elderly subjects.

The psychomotor and cardiovascular effects of minaprine 100 mg, a novel antidepressant, were compared with amitriptyline 25 mg, as a positive control, and placebo in a single dose randomised double-blind crossover trial using an automated psychomotor test battery (APT), postural sway (PS), blood pressure (BP) and pulse in nine young and nine elderly healthy subjects. Analysis of variance, taking into account baseline values, showed that continuous attention test (CAT), critical flicker fusion threshold (CFFT), decision making test (DMT) and paired word association (PWA) were significantly impaired with amitriptyline compared with minaprine and placebo. Minaprine did not differ from placebo. Amitriptyline significantly lowered supine systolic blood pressure (BP) and all treatments produced significant decreases in heart rate in young and elderly. No age effect on psychomotor performance was seen. Minaprine compared favourably with amitriptyline using the APT with the doses used. The APT is useful in the evaluation of new drugs on psychomotor performance.

Adult↗

A comparative study of cyproheptadine and DL carnitine on psychomotor performance and memory in healthy volunteers.

This study was performed in order to investigate the extent and severity of cyproheptadine effects on psychomotor performance, mood and memory functions and to compare them to the effects of DL carnitine, another appetite stimulant. Twelve healthy volunteers received 2 doses (at 800 am and 1200 am) of 6 mg cyproheptadine, 1600 mg DL carnitine and placebo on separate days at a weekly intervals. The study followed a double-blind, latin-square design. Assessment of dependent variables was performed 1 h after the first and 1 h and 5 h after the second administration of the drug. On each of these occasions, the following measurements were performed: choice reaction time (CRT), critical flicker fusion (CFF), digit symbol substitution test (DSST), short-term memory (paired words association test), long-term memory (picture test) and 100 mm visual analogue scales of subjective ratings (VAS). Cyproheptadine significantly impaired objective measures (CFF) and subjective ratings both at 1 h and 5 h after the second dosage. Compared with cyproheptadine, DL carnitine induced a slight improvement in psychomotor performance as assessed by CRT. None of the drugs had any effect on memory and on appetite at the doses studied. In conclusion, cyproheptadine at usual doses had a sedative effect, the intensity and duration of which implied a certain risk in performing daytime functions eg when driving, or manipulating machines. DL carnitine had no effect on vigilance.

Adult↗

Next day effects of a normal night's drinking on memory and psychomotor performance.

AIM: To investigate in social drinkers the effects of a 'normal' evening of drinking alcohol on cognitive performance. METHODS: Aiming for ecological validity, the study required participants to consume their usual quantity of any type of alcoholic beverage in their chosen company (hangover situation). However, the timing of drinking was restricted to the period between 22:00 and 02:00 hours on the night before testing. Testing included memory and psychomotor performance tests; testing was also performed after an evening of abstinence (no hangover situation), following a counterbalanced design using repeated measures, with time of testing (09:00, 11:00 and 13:00 hours) and order of testing (hangover/no hangover; no hangover/hangover) as 'between participant' factors in the analysis. RESULTS: Forty-eight social drinkers (33 women, 15 men) aged between 18 and 43 years were tested, with a 1-week interval between test sessions. The morning after alcohol (mean consumption: 14.7 units for men; 10.4 units for women), free recall was impaired at 09:00 hours and delayed recognition and psychomotor performance were impaired throughout the morning, despite blood alcohol levels of zero or very near zero. CONCLUSION: Memory and psychomotor performance is impaired on the morning after heavy 'social' drinking.

Adolescent↗

Effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol.

RATIONALE: Sleep deprivation has a negative effect on cognitive and psychomotor performance and mood state, partially due to decreases in creatine levels in the brain. Therefore, creatine supplementation should lessen the negative effects of sleep deprivation. OBJECTIVES: The objective of this study was to examine the effect of creatine supplementation and sleep deprivation, with mild exercise, on cognitive and psychomotor performance, mood state, and plasma concentrations of catecholamines and cortisol. METHOD: Subjects were divided into a creatine group (n=10) and a placebo group (n=9). They took 5 g of creatine monohydrate or a placebo, dependent on their group, four times a time a day for 7 days, immediately prior to the experiment. The study was double blind. Subjects undertook tests of random movement generation (RMG), verbal and spatial recall, choice reaction time, static balance and mood state pre-test (0 h), after 6, 12 and 24 h of sleep deprivation, with intermittent exercise. They were tested for plasma concentrations of catecholamines and cortisol at 0 and 24 h. RESULTS: At 24 h, the creatine group demonstrated significantly less change in performance from 0 h (delta) in RMG, choice reaction time, balance and mood state. There were no significant differences between groups in plasma concentrations of catecholamines and cortisol. Norepinephrine and dopamine concentrations were significantly higher at 24 h than 0 h, but cortisol were lower. CONCLUSIONS: Following 24-h sleep deprivation, creatine supplementation had a positive effect on mood state and tasks that place a heavy stress on the prefrontal cortex.

Adult↗

Perioperative effects of melatonin and midazolam premedication on sedation, orientation, anxiety scores and psychomotor performance.

BACKGROUND AND OBJECTIVE: To compare the perioperative effects of melatonin and midazolam given in premedication, on sedation, orientation, anxiety scores and psychomotor performance. METHODS: Exogenous administration of melatonin not only facilitates the onset of sleep but also improves its quality. A prospective, randomized, double-blind, placebo-controlled study was performed in 66 patients undergoing laparoscopic cholecystectomy. Patients were given melatonin 5 mg, midazolam 15 mg or placebo, 90 min before anaesthesia, sublingually. Sedation, orientation and anxiety were quantified before; 10, 30, 60 and 90 min after premedication; and 15, 30, 60 and 90 min after admission to the recovery room. Neurocognitive performance was evaluated at these times, using the Trail Making A and B and Word Fluency tests. The differences between the groups were analysed by ANOVA. Two-way comparisons were performed by Scheffé analysis. Sedation and amnesia were analysed by the chi2 test. RESULTS: Patients who received premedication with either melatonin or midazolam had a significant increase in sedation and decrease in anxiety before operation compared with controls. After operation, there was no difference in sedation scores of all groups. Whereas, 30, 60 and 90 min after premedication the melatonin and midazolam groups exhibited a significantly poorer performance in Trail Making A and B tests compared with placebo, there were no significant differences among the groups in terms of neuropsychological performance after the operation. Amnesia was notable only in the midazolam group for one preoperative event. CONCLUSION: Melatonin premedication was associated with preoperative anxiolysis and sedation without postoperative impairment of psychomotor performance.

Adult↗

Effects of sulphur hexafluoride on psychomotor performance.

The narcotic influence of sulphur hexafluoride on mental and psychomotor performance has been studied in 9 subjects at normal atmospheric pressure. Control experiments were performed with air and with nitrous oxide. Psychomotor, perceptual and cognitive abilities were assessed using a computerized test battery. Subjects were exposed to air and six different normoxic gas mixtures: 13, 26, and 39% N2O, and 39, 59, and 79% SF6. Significant performance impairments were found with 13% N2O and gradual further impairment with 26, and 39% N2O. During exposure to 39, 59, and 79% SF6 over-all performance was impaired by 5, 10, and 18%, respectively. Impairment was significant with 59 and 79% SF6. The results indicate that the relative narcotic potency of SF6: N2O is about 1:4 in humans. It is concluded that a normoxic SF6-O2 mixture can be inhaled for lung function studies without any harmful effects and that the short-lasting narcotic effect, although detectable with a test battery, would not impair the ability of the subject to perform simple breathing procedures.

Adult↗

Effects of mizolastine, a new antihistamine, on psychomotor performance and memory in elderly subjects.

The effects of a single 10 mg dose of the new H1 antihistamine mizolastine on psychomotor performance and memory in the elderly were assessed in a double-blind, cross-over, placebo-controlled study in 15 elderly female volunteers aged 66-77 years, using clemastine 2 mg as a positive control. Objective (critical flicker fusion, choice reaction time, digit symbol substitution, immediate and delayed free recall) and subjective (linear analogue rating scales) assessments were done on each test day before the dose, then 4 and 8 h post-dose. Plasma samples were also collected. A single oral dose of mizolastine within the range of recommended daily therapeutic dosages (10 mg) failed to induce subjective drowsiness and produced no detrimental effects on psychomotor performance or on short-term and long-term memory in the elderly subjects. In contrast, 2 mg clemastine induced significant impairments (decrease in critical flicker fusion, increase in recognition reaction time) in comparison with placebo and mizolastine, although it did not impair memory. The pharmacokinetic profile of mizolastine in the elderly study subjects was similar to that observed in healthy young volunteers. Therefore, it can be concluded that mizolastine 10 mg could be used safely in elderly out-patients as it preserves functions involved in activities of daily living.

Aged↗

Lack of amnestic, psychotomimetic or impairing effect on psychomotor performance of eliprodil, a new NMDA antagonist.

The possible effects on memory, psychomotor performance and mood of eliprodil, a new non-competitive NMDA receptor antagonist acting through the polyamine modulatory site, was assessed in a randomized, double-blind, cross-over, placebo-controlled study involving 11 healthy young male volunteers. Eliprodil 30 mg, a placebo and midazolam 15 mg, a positive control, were administered as a single oral dose at 1 week wash-out intervals. Objective tests evaluated both memory (Sternberg memory scanning and paired words for short-term memory, delayed free recall of pictures for long-term memory) and psychomotor functions and arousal (critical flicker fusion threshold, choice reaction time, body sway). Mood was assessed using self-ratings (LARS, POMS, ARCI). Statistical analysis was performed using an ANOVA with pairwise comparisons using Tukey's method. A single dose of eliprodil 30 mg was free of any detrimental effect on memory and skilled performance and did not produce either subjective sedation or excitation or psychotomimetic effects in comparison with placebo. In contrast, a single dose of midazolam 15 mg induced a marked impairment in psychomotor performance and cognitive functions (significant reduction in CFF, increase in CRT and body sway, disruption of short- and long-term memory). The potent sedative activity of midazolam, peaking 1 to 3 h post-dose, was confirmed by subjective evaluation and had disappeared 8 h post-dose.

Adult↗

The effects of alcohol and other drugs on psychomotor performance and cognitive function.

The effects of four doses of alcohol (0.25 g/kg-1 g/kg) and placebo on a standard test battery of cognitive and psychomotor performance are described. The tests included critical flicker fusion threshold, choice reaction time, tracking and memory scanning. The results of this experiment are compared with those of a number of similar studies which examined the effects of other psychoactive substances. Using relative effect sizes, the behavioural toxicity of alcohol is compared with the effects of these other drugs on psychomotor performance and cognitive function.

Adult↗

Comparative effects of zopiclone, triazolam and placebo on memory and psychomotor performance in healthy volunteers.

This study evaluated the effects of acute doses of zopiclone (7.5 mg), triazolam (0.25 mg) and placebo on memory and psychomotor performance of 12 normal volunteers. The subjects received both drugs in a repeated measure, double-blind Latin square design. The tests (CFF, CRT, DSST, memory assessments) were performed before and 2 and 6 hr after treatment. Zopiclone and triazolam induced an anterograde amnesia affecting short-term and long-term memory which lasted less than 6 hr. No retrograde amnesia was observed. Two hr after drug intake of both hypnotics psychomotor performances were significantly altered compared with placebo. The subjects also felt more drowsy, dizzy, clumsy and tired, and less alert and energetic 2 hr after zopiclone and triazolam compared to placebo. There was no difference between the effects of the two hypnotics at the doses studied.

Adult↗

The impact of bupropion on psychomotor performance.

INTRODUCTION: The NDRI (noradrenalin-dopamine re-uptake inhibitor) bupropion SR (sustained-release) is marketed as Wellbutrin* for treatment of depression or Zyban as a smoking cessation aid. There has been considerable interest in the possibility of returning aircrew to restricted flying duties once stabilized on bupropion SR after resolution of depressive symptoms, or while taking bupropion SR for smoking cessation. This study was undertaken to determine whether bupropion SR affects psychomotor performance. METHOD: There were 24 subjects (18 men and 6 women) who were assessed for psychomotor performance during placebo and bupropion SR treatment in a double-blind cross-over in counter-balanced order. Each treatment arm lasted 5 wk. The daily bupropion SR dose was 150 mg during week 1, and 300 mg during weeks to 2 to 5. Subjects completed a drug side-effect questionnaire and were tested on two psychomotor test batteries once per week during each of the placebo and drug arms. RESULTS: There was no significant Impact of bupropion SR on serial reaction time, logical reasoning, serial subtraction, or multitask performance. With respect to drug side effects there was a main effect of drug on "number of awakenings" (p < 0.048), "difficulty returning to sleep" (p < 0.004), and "dry mouth" (p < 0.049). There was no impact of bupropion SR on dizziness. DISCUSSION: While we found some of the expected side effects due to bupropion SR, there was no effect on psychomotor performance. These findings support the possibility of returning aircrew to restricted flight duties (e.g., in non-fast jet aircraft) under close observation once stabilized on bupropion SR.

Adult↗

The effects of midazolam in conjunction with alcohol on sleep, psychomotor performance and car driving ability.

The acute and early morning effects of midazolam 15mg and alcohol 0.5g/kg on subjective measures of CNS activity, psychomotor performance and car driving ability were investigated in eight healthy female volunteers. One hour following treatment with midazolam and midazolam + alcohol, critical flicker fusion threshold (CFFT) was significantly depressed and subjects perceived themselves as feeling more sedated when compared to treatment with placebo or alcohol alone. Perceived ease of getting to sleep (GTS) was also improved by midazolam and the midazolam + alcohol combination. Stimulus processing time was significantly increased at one hour after treatment by midazolam taken in conjunction with alcohol, thus resulting in an overall increase in total reaction time. On the morning following administration, both "on the road" assessments of car driving ability and laboratory tests of psychomotor performance were unaffected by any of the treatment conditions. Midazolam 15mg was found to be an effective sleep inducer with no evidence of residual or "hangover" effects, although the drug's hypnotic activity may be augmented by social doses of alcohol.

Adult↗

The effects of subanesthetic concentrations of sevoflurane and nitrous oxide, alone and in combination, on analgesia, mood, and psychomotor performance in healthy volunteers.

UNLABELLED: We studied the effects of subanesthetic concentrations of sevoflurane and nitrous oxide, alone and in combination, on analgesia, mood, and psychomotor performance in human volunteers. We hypothesized that nitrous oxide and sevoflurane would produce both opposing and potentiating effects within the same study. Over the course of three sessions, 20 subjects inhaled 0%, 0.2%, or 0.4% end-tidal sevoflurane for a 68-min period that was divided into four 17-min blocks. During either the second or fourth block, 30% end-tidal nitrous oxide was added to the concentration of sevoflurane being inhaled. Pain response, psychomotor performance, and mood were evaluated during the second and fourth blocks. Pain ratings were higher when sevoflurane and nitrous oxide were administered together than when nitrous oxide was administered alone, which indicates that sevoflurane attenuated the analgesic effects of nitrous oxide. Sevoflurane increased self-reported ratings of sleepiness, and the addition of nitrous oxide decreased these ratings. Nitrous oxide potentiated psychomotor impairment that was induced by sevoflurane. The combination of sevoflurane and nitrous oxide produced both opposing and potentiating effects within the same study. The results suggest that nitrous oxide and sevoflurane may act through different neurochemical mechanisms on some end points, such as analgesia and sleepiness. IMPLICATIONS: Healthy volunteers inhaled subanesthetic concentrations of sevoflurane and nitrous oxide. Sevoflurane made nitrous oxide less effective as an analgesic, and nitrous oxide made sevoflurane less effective as a sedative. The two drugs may work at cross purposes on different end points of anesthesia.

Adult↗

Motion-sickness medications for aircrew: impact on psychomotor performance.

INTRODUCTION: Motion sickness remains a significant problem for aircrew both in the flying environment (airsickness) and for aircrew deployed at sea (seasickness). While some anti-motion-sickness medications provide reasonable efficacy, adverse neurocognitive effects limit their use in military personnel engaged in safety-sensitive operational roles such as flying. The purpose of this study was to assess the impact on psychomotor performance of promethazine, meclizine, and dimenhydrinate and to determine if the addition of pseudoephedrine or damphetamine to promethazine would ameliorate its adverse effects. METHODS: There were 21 subjects (11 men, 10 women), aged 22-59, who were assessed for psychomotor performance on 4 tasks as well as with sleepiness and drug side-effects questionnaires. Psychomotor testing was conducted prior to, and for 7 h after, ingestion of a single dose of each of placebo, promethazine 25 mg, meclizine 50 mg, dimenhydrinate 50 mg, promethazine 25 mg plus pseudoephedrine 60 mg, and promethazine 25 mg plus d-amphetamine 10 mg. RESULTS: Relative to placebo, promethazine, meclizine, and promethazine plus pseudoephedrine impaired performance on all four tasks [serial reaction time (SRT), logical reasoning (LRT), serial subraction (SST), and multitask (MT)]. Dimenhydrinate impaired performance on the SRT only. Promethazine plus d-amphetamine did not impair performance on any task nor did it result in increased sleepiness. The times to recovery of normal performance for SRT with promethazine, meclizine, dimenhydrinate, and promethazine plus pseudoephedrine were > 7.25, 7.25, 4.25, and 7.25 h, respectively; for LRT were > 7.25, > 7.25, ns, and 7.25 h; for SST were > 7.25, > 7.25, ns, and 7.25 h; for MT were 7.25, 7.25, ns, and 7.25 h. Recovery times to baseline sleepiness levels for promethazine, meclizine, dimenhydrinate, and promethazine plus pseudoephedrine were 7.25, > 7.25, 6.25, and > 7.25 h. CONCLUSION: Only promethazine plus d-amphetamine was free from impact on psychomotor performance and did not increase sleepiness.

Adult↗