Effects of single and multiple doses of a new reversible MAO-A inhibitor,befloxatone, on psychomotor performance and memory in healthy subjects

The effects on memory, psychomotor performance and mood of two dosage regimens of befloxatone, a new reversible and selective MAO-A inhibitor were assessed in a randomized, double-blind, cross-over, placebo-controlled study involving 12 healthy young male volunteers. Befloxatone and a placebo were orally administered as single (5 and 10 mg) and repeated doses (10 mg once daily and 5 mg twice daily) at one week wash-out intervals. Objective tests evaluated both memory (working memory, immediate and delayed free recall of a word list, dual coding and faces recognition) and vigilance continuous performance task (CPT), and digit symbol substitution (DSST). Subjective mood and sleep were assessed using visual analogue scales and the Leeds Sleep Evaluation Questionnaire. Statistical analysis was conducted using an ANOVA with pairwise comparisons using the Student Newman Keuls procedure. Both dosage regimens of befloxatone (10 mg once daily or 5 mg twice daily) were free of any detrimental effect on vigilance (CPT) and information processing (DSST) and did not significantly disrupt short- and long-term memory (working memory, free recall of words, dual coding and faces recognition). In addition, no subjective sedation or sleep disturbances were recorded. In conclusion, this study gives no evidence to suggest that befloxatone, at a daily dose which shows potent MAO-A inhibition, has any sedative or amnestic properties likely to interfere with the activities of everyday-life in young subjects and therefore may be safely administered in depressed outpatients.     

The effects of reboxetine and amitriptyline, with and without alcohol on cognitive function and psychomotor performance

Reboxetine is a novel antidepressant that has been shown to be effective in the treatment of major depressive disorders. The present experiment was designed to assess whether it affects the cognitive and psychomotor skills necessary for optimum function in everyday life. Ten healthy male volunteers received reboxetine 0.5  mg, 1  mg or 4  mg, amitriptyline 25  mg, or matched placebo with and without alcohol (0.6  mg  kg⁻¹) in a double-blind 10-way crossover study. A psychometric test battery was administered at baseline and at 1, 2.25, 3.5, 6 and 9  h post-dose. The results showed that reboxetine had little or no effect on performance at any dose, compared with placebo. Amitriptyline, however, with and without alcohol, lowered critical flicker fusion threshold compared with placebo and/or reboxetine at all test points (e.g. at 3.5  h: 28.51   vs 30.33  Hz; P <0.05); increased reaction time (e.g. 619   vs 540  ms; P <0.05); increased tracking error (e.g. 16.34 vs 8.54 RMS units; P <0.05); and slowed short-term memory scanning (e.g. 742 vs 590  ms; P <0.05). It is concluded that reboxetine at doses of 4  mg and below is free from disruptive effects on cognitive function and psychomotor performance, and that it does not act synergistically with alcohol, in contrast to amitriptyline.     

Lack of interaction between two antihistamines,mizolastine and cetirizine,and ethanol in psychomotor and driving performance in healthy subjects

The pharmacodynamic interaction between mizolastine, a new H₁ antihistamine, and ethanol was assessed in a randomized, double-blind, three-way crossover, placebo-controlled study. Eighteen healthy young male volunteers received mizolastine 10 mg, or cetirizine 10 mg or placebo once daily for 7 days with a 1-week wash-out interval. An oral dose of ethanol or ethanol placebo, given 2 h after dosing on days 5 or 7 of each treatment period, was administered to achieve a peak blood alcohol concentration (BAC) of 0.7 g/l, then maintained for 1 h by two further doses of ethanol. Driving ability and psychomotor performance were evaluated using actual and simulated driving tests, critical flicker fusion threshold (CFF), adaptive tracking and divided attention (DAT) tasks. Ethanol produced a significant decrement in all tasks up to 5.5 h after administration: an increase in steering movements of 4.6, in lateral deviation of 0.45 m, in braking reaction time of 80 ms, in driving test and DAT performance of +3.2; and a decrease in CFF and in tracking speed of 2.6 m·s^–1. Neither mizolastine nor cetirizine significantly impaired driving ability or arousal (CFF) compared with the placebo. However, both drugs significantly impaired DAT performance 6:00 h post-dose (increase of +2.1 for mizolastine and +2.4 for cetirizine). The tracking speed was significantly decreased 7:50 h after mizolastine administration (-1.3 m·s^–1) and more consistently from 1:30 to 7:50 h after cetirizine administration (-1.4 m·s^–1). No significant adverse interaction, i.e potentiation, occurred between ethanol and either antihistamine. No pharmacokinetic interaction occurred in BAC. In conclusion, treatment with a therapeutic dose of mizolastine or cetirizine has minimal or no effect on human performance, does not impair driving task performance and does not interact with ethanol at concentrations of 0.7 g·^–1.     

Comparative study of acute effects of single doses of fexofenadine, olopatadine, d-chlorpheniramine and placebo on psychomotor function in healthy volunteers

Since most classical (first-generation) antihistamines have undesirable sedative effects on the central nervous system (CNS), newer (second-generation) antihistamines have been developed to relieve the sedative effects and to improve the patient's quality of life. However, the psychomotor profiles of second-generation antihistamines are not fully elucidated. In this randomized, double-blind, crossover study, the acute effects of single doses of second-generation antihistamines, fexofenadine (120 mg) and olopatadine (10 mg), on cognitive and psychomotor performance were investigated in comparison with those of placebo and d-chlorpheniramine (4 mg), a first-generation antihistamine, using objective and subjective assessments, in 11 healthy Japanese volunteers. In a battery of psychomotor tests, d-chlorpheniramine impaired tracking ability in the compensatory tracking task and caused a reduction in behavioural activity as continuously measured by wrist actigraphy. Olopatadine, like d-chlorpheniramine, reduced the behavioural activity, while fexofenadine had no effect in any of the tests. No significant changes in the subjects' self-ratings of drowsiness were found with the three antihistamines. These results suggest that d-chlorpheniramine and olopatadine, but not fexofenadine, produce sedative effects on psychomotor performance, and that the CNS profile of fexofenadine is different from that of olopatadine.     

Effect of combined atenolol and nifedipine administration on psychomotor performance in normal subjects

The aim of the present study was to evaluate the central effects of single doses of the -adrenoceptor antagonist atenolol and the calcium antagonist nifedipine retard, alone and in combination, in normal subjects. Twelve normal males received single oral doses of atenolol 100 mg, nifedipine retard 20 mg, atenolol 100 mg and nifedipine retard 20 mg in combination, diazepam 5 mg (active control), and each of two matching placebos in a double-blind, randomised fashion. Psychomotor performance was assessed using digit symbol substitution, letter cancellation (LCT), continuous attention, choice reaction time, finger tapping, immediate recall and short-term memory. Two flash fusion and critical flicker fusion thresholds were measured and subjective assessments made using visual analogue scales (VAS). Diazepam 5 mg significantly worsened LCT scores at 4h, significantly impaired alertness at 2 h and 4 h, and tended to increase reaction time and impair continuous attention and physiological measurements. Atenolol 100 mg alone significantly reduced alertness at 2 h and 4 h, and also tended to impair physiological measurements. Nifedipine retard 20 mg produced no significant psychomotor effects. Combined atenolol and nifedipine retard administration produced a small but significant improvement in continuous attention and a reduction in body sway, with no adverse effects being evident on performance or subjective awareness. The results suggest that no significant adverse effects on psychomotor performance are produced by single doses of atenolol 100 mg and nifedipine retard 20 mg when given together in normal subjects. The combination may therefore be useful in the treatment of hypertensive patients requiring dual therapy, and in whom adverse central effects are of particular importance.This paper was presented and accepted for publication in abstract form at the British Pharmacological Society, University of Bradford, July 1993.     

The effects of repeated doses of clomipramine and alprazolam on physiological,psychomotor and cognitive functions in normal subjects

Summary The effects of a 10 day administration of clomipramine (25–50 mg t.i.d.), alprazolam (0.25–0.75 mg t.i.d.) and placebo were assessed in normal volunteers in a double-blind cross-over study. A battery of physiological, psychomotor and cognitive tests was administered both before and 3 h after drug on days 1, 5 and 10.The effects of alprazolam on EEG and evoked potentials were characteristic of benzodiazepines; clomipramine had little effect. In contrast, reaction speed was markedly slowed by clomipramine but little affected by alprazolam.Neither drug produced any accumulation of effect on a verbal recall task but neither did tolerance develop to the acute impairments produced by active treatments. Alprazolam produced an increase in levels of forgetting, especially on day 5. Subjective ratings for mood and bodily symptoms were adversely affected by clomipramine but little altered by alprazolam.It is suggested that some of the differences between drug treatments may be due to differences in the speed of onset of tolerance.     

Suriclone enhances the actions of chlorpromazine on human psychomotor performance but not on memory or plasma prolactin in healthy subjects

Twelve healthy subjects received single oral doses of 0.4 mg suriclone (SU), 7.5 mg zopiclone (ZO) and placebo, alone and together with 50 mg chlorpromazine (CP), double blind and crossover, in Latin square order, at one-week intervals. Performance tests administered before and 1.5, 3.5 and 6 h after drug intake included digit symbol substitution and simulated driving combined in a Global test, flicker fusion frequency, body balance and memory and subjective assessments. Changes from baseline were examined statistically. Performance and memory data were analysed from only 11 subjects.Compared to placebo, SU minimally affected global performance, although it slowed reactions and tended to impair digit substitution. ZO impaired global performance at 1.5 h, affected performance in several separate tests, and produced subjective muzziness. CP did not impair global performance, although it did impair digit substitution and render the subjects drowsy, weak and dreamy. The combinations SU + CP and ZO + CP definitely impaired global performance more than CP alone. This difference was also found in most objective tests but less so in the subjective tests.CP and its combinations produced similar increases in plasma prolactin. Active drugs and their combinations variably lowered blood pressure and increased heart rate, and one subject collapsed after CP. The treatments irregularly impaired spatial memory and learning acquisition.No pharmacokinetic interactions were seen in the plasma levels of suriclone, zopiclone and chlorpromazine. The impairment of performance after these combinations resembles that previously encountered after 2.5 mg lorazepam, or 15 mg diazepam +100 mg remoxipride.     

Lack of interaction between amisulpride and lorazepam on psychomotor performance and memory in healthy volunteers

The potential pharmacodynamic interaction between amisulpride (a benzamide-type antipsychotic) and lorazepam was evaluated in a randomized, double-blind, cross-over, placebo-controlled study involving 18 healthy caucasian male volunteers, aged 18–35 years. They received single doses of amisulpride 50 mg and 200 mg. The interaction of the drug with a single oral dose of lorazepam 2 mg was assessed on six 1-day treatment periods separated by wash-out periods of 1 week. Pharmacodynamic criteria were: critical flicker fusion frequency, multiple choice reaction time, tapping, body sway, arithmetic calculation, Buschke's test for short and long term memory and self-ratings by ARCI scale. Prolactin as assayed for each treatment period. Statistical analysis was performed using a 3-way ANOVA. For psychometric tests and body sway, analyses were evaluated on changes from baseline. For memory test, analyses were done on raw data. Amisulpride alone, at single oral dose of 50 mg and 200 mg, was devoid of any clinically relevant impairment psychometric tests, short term and long term memory and mood. A single oral dose of lorazepam 2 mg induced marked impairment in psychometric performances, which all, except CFF test, were severely affected. Disturbances were also recorded in memory tests, and in subjective sensation (ARCI). The peak effects were 2–4 h after administration, but the majority of results were also affected up to 8 h. Prolactin levels were increased after either dose of amisulpride, but not after placebo or lorazepam. The co-administration of amisulpride plus lorazepam induced a prolactin elevation equivalent to that of amisulpride alone. In conclusion, the co-administration of amisulpride, at both doses of 50 mg and 200 mg, did not potentiate nor antagonize the detrimental effect of lorazepam 2 mg on pharmacodynamic parameters. © 1998 John Wiley & Sons, Ltd.     

The effects of brofaromine alone and in conjunction with alcohol on cognitive function,psychomotor performance,mood and sleep in healthy volunteers

Brofaromine is a novel antidepressant that functions by the inhibition of the A form of monoamine oxidase (MAO). This inhibition is reversible, making brofaromine both pharmacologically and structurally different from most of the currently available MAO inhibitors. The drug has been shown to be clinically effective and to have significantly fewer problems than other MAO inhibitors in terms of hepatic toxicity and interaction with tyramine and coadministered tricyclic antidepressants. The present experiment was designed to assess the behavioural toxicity of the drug. Seventeen normal volunteers received brofaromine 50 mg or 75 mg, amitriptyline 50 mg or placebo with and without alcohol in a double blind eight-way crossover study. A psychometric test battery was administered at 3, 6 and 12 h post-dose. The results show that brofaromine had little or no effect on the measures employed, compared to placebo. The amitriptyline verum (with and without alcohol) however lowered critical flicker fusion threshold compared to placebo at all test points, increased reaction time, increased tracking error, and slowed memory scanning. It is concluded that, in volunteers, acute doses of brofaromine are free from disruptive effects on cognitive function and psychomotor performance, in contrast to both amitriptyline and alcohol which showed debilitating effects on most of the measures employed.     

Effects of acute and repeated doses of two muscle relaxants chlormezanone and thiocolchicoside,on vigilance and psychomotor performance of healthy volunteers

This was a randomized double blind, placebo-controlled cross over study performed on 12 healthy female volunteers. It consisted of three treatment sessions of 7 days separated by a one week wash out period. The objectives of the study were to assess the sedative activity of 2 muscle relaxant drugs: chlormezanone (600 mg daily) and thiocolchicoside (16 mg daily) after a single oral administration and at steady state (day 7). The drugs were administered orally, during each treatment period as 3 capsules daily for 7 days. Assessment criteria explored psychometric tests, body sway and subjective feeling rating scales. Chlormezanone induced objective disturbances of vigilance and concentration characterised by a decrease in the performance of an arithmetic calculation test and an increase in body sway area recorded in comparison with thiocolchicoside and placebo. These impairments were mainly marked on steady state. Most of the volunteers (10 over 12) complained of drowsiness throughout this treatment. Thiocolchicoside was devoided of any objective or subjective sedative side effect.     

Evaluation of the cognitive, psychomotor and pharmacokinetic profiles of rupatadine, hydroxyzine and cetirizine, in combination with alcohol, in healthy volunteers

INTRODUCTION: The Central Nervous System (CNS) impairment induced by moderate alcohol (ALC) ingestion may be enhanced if other drugs are taken simultaneously. Rupatadine (RUP) is a new H(1)-antihistamine which also inhibits platelet activating factor (PAF) release in inflammatory reactions. OBJECTIVE: The main aim of the study was to assess the effects of ALC 0.8 g/Kg on RUP (10 mg and 20 mg) CNS effects. An evaluation of alcohol and RUP pharmacokinetics was also attained. METHODS: Eighteen healthy young volunteers of both sexes participated in a phase I, randomised, crossover, double-blind, placebo-controlled study. At 2-week intervals they received six treatments: (a) placebo (PLA), (b) ALC alone and ALC in combination with: (c) hydroxyzine 25 mg (HYD), (d) cetirizine 10 mg (CET), (e) RUP 10 mg or (f) RUP 20 mg. At baseline and several times thereafter, seven psychomotor performance tests (finger tapping, fine motoric skills, nystagmus, temporal estimation, critical-flicker-fusion frequency, 'd2' cancellation, simple reaction) and eleven subjective self-reports (drunkenness, sleepiness, alertness, clumsiness, anger, inattentiveness, efficiency, happiness, hostility, interest and extraversion) were carried out. Two-way (treatment, time) ANOVAs for repeated measures to each variable together with a multivariate non-parametric approach were applied. Plasma concentrations of alcohol, and of RUP and its metabolites, were quantified by validated immunofluorescence and LC/MS/MS methods, respectively. Plasma-time curves for all compounds were analysed by means of model-independent methods. RESULTS: The combination of alcohol with HYD, CET and RUP 20 mg produced more cognitive and psychomotor impairment as compared to alcohol alone, being the combination of alcohol and HYD the one which induced the greatest deterioration. The combination of alcohol and RUP 10 mg could not be differentiated from ALC alone. Subjective self-reports reflect effects on metacognition after the combination of alcohol with HYD and CET i.e. the increased objective impairment observed was not subjectively perceived by the subjects. No significant differences were obtained when comparing alcohol plasma concentrations assessed after the treatments evaluated. RUP showed a lineal kinetic relationship after 10 and 20 mg with a higher exposition to both metabolites assayed. CONCLUSIONS: Present results showed that single oral doses of rupatadine 10 mg in combination with alcohol do not produce more cognitive and psychomotor impairment than alcohol alone. Higher doses of rupatadine, in combination with alcohol, may induce cognitive and psychomotor deterioration as hydroxyzine and cetirizine at therapeutic doses.     

ALDH2 genotype-associated differences in the acute effects of alcohol on P300, psychomotor performance, and subjective response in healthy young Korean men: a double-blind placebo-controlled crossover study

BACKGROUND: This study investigated the acute effects of alcohol on neurophysiological and psychomotor functions and the subjective response in healthy young Korean men according to the mitochondrial aldehyde dehydrogenase (ALDH2) genotype. METHOD: A total of 24 males, half with ALDH2*1/*1 (active form) and the rest with ALDH2*1/*2 (inactive form), were selected through genotyping. In a double-blind placebo-controlled crossover design, each subject consumed either a 0.5 g/kg dose of alcohol or a placebo on two separate occasions, 1 week apart. The blood alcohol concentrations (BACs), P300 of event-related potential, psychomotor performance, and perceived feelings were assessed. RESULTS: Although the BACs were similar between the two groups, the effects of alcohol on P300 were greater overall in subjects with ALDH2*1/*2 than in subjects with ALDH2*1/*1. Psychomotor performance was more impaired after alcohol ingestion in subjects with ALDH2*1/*2 than in subjects with ALDH2*1/*1. The subjective response after alcohol ingestion was more negative in subjects with ALDH2*1/*2, compared to subjects with ALDH2*1/*1. CONCLUSIONS: These results suggest that the ALDH2 polymorphism is an important factor in determining the effects of alcohol on various psychobehavioral functions.     

The psychomotor and cognitive effects of a new antihistamine,mizolastine, compared to terfenadine,triprolidine and placebo in healthy volunteers

Eighteen healthy volunteers received mizolastine 5 mg, 15 mg or 45 mg, terfenadine 60 mg, triprolidine 10 mg or placebo in a 6-way crossover, double blind study. Following each dose, subjects performed a series of tests of cognitive function and psychomotor performance at 1, 3, 5, 8 and 24 hours post-dose. The test battery included critical flicker fusion, choice reaction time, tracking, Stroop and Sternberg memory tests and assessment of subjective sedation.Sedative effects and a concomitant reduction in psychomotor and cognitive function were observed following triprolidine, terfenadine and the highest dose of mizolastine, 45 mg, e.g. triprolidine reduced CFF threshold by 1.5 Hz and increased reaction time by 50 ms, impairments comparable to those caused by blood alcohol concentrations of 50 mg%, the legal limit in many countries. Mizolastine 5 mg did not differ significantly from placebo and at 15 mg differed only at one test point at one time.It may be concluded that mizolastine (5 mg and 15 mg) is free from disruptive effects on cognitive function and psychomotor performance, in contrast to terfenadine 60 mg, triprolidine 10 mg and mizolastine 45 mg.     

Lack of effect of single and repeated doses of levocetirizine,a new antihistamine drug,on cognitive and psychomotor functions in healthy volunteers

Aims  Levocetirizine (R-cetirizine), is the active enantiomer of cetirizine, an antihistamine indicated in the treatment of allergic rhinitis and chronic idiopathic urticaria. The purpose of this trial was to analyse the effects of levocetirizine single and multiple doses on CNS using integrated measures of cognitive and psychometric performance.
Methods  A battery of psychometric tests was used: critical flicker fusion (CFF), choice reaction time (CRT), body sway (BS), learning memory test (LMT) and subjective assessments of alertness compared with placebo. Nineteen (19) healthy male volunteers received either levocetirizine 5 mg (therapeutic dose), diphenhydramine 50 mg or placebo once daily for 5 consecutive days (3-way cross-over). Diphenhydramine was used as a positive control. CFF tests were performed on days 1 and 5 at baseline and up to 24 h following drug intake. Subjects used the Bond-Lader visual analogue scales (VAS) to assess their mood and vigilance.
Results  In contrast to diphenhydramine, when compared with placebo, levocetirizine did not modify the CFF (primary endpoint), regardless of the dosing scheme (−1.62 Hz [−2.61, −0.64] and −0.81 Hz [−1.80, 0.19], respectively, 3 h after dosing on day 1). CRT was decreased with both levocetirizine and placebo up to 5 h after dosing on day 1 and up to 3 h after dosing on day 5. Body sway data were similar with levocetirizine and placebo but increased with diphenhydramine. LMT was similar in all three groups. No relevant difference between placebo and levocetirizine was recorded by the subjects on their assessment of alertness using the VAS, whilst decreased alertness was reported following diphenhydramine 50 mg.
Conclusions  This study showed that levocetirizine does not produce any deleterious effect on cognitive and psychometric functions compared with placebo in healthy male volunteers.     

A double-blind, placebo-controlled investigation of the residual psychomotor and cognitive effects of zolpidem-MR in healthy elderly volunteers

AIM: To assess residual psychomotor and cognitive effects of a modified-release formulation of zolpidem (zolpidem-MR), developed to provide sustained hypnotic efficacy during the whole night, compared with placebo and flurazepam. METHODS: Twenty-four healthy elderly volunteers received four study treatments (zolpidem-MR 6.25 mg and 12.5 mg, placebo and flurazepam 30 mg) using a randomized, cross-over, double-blind design. Residual psychomotor and cognitive effects were assessed with a psychometric test battery. Quality of sleep and residual effects were evaluated subjectively with the Leeds Sleep Evaluation Questionnaire. RESULTS: Psychometric performance was significantly impaired with flurazepam but not with zolpidem-MR at either dose. Ease of falling asleep and sleep quality were significantly improved with both doses of zolpidem-MR and with flurazepam. Neither active drug modified perception of well-being on awakening. CONCLUSION: In elderly subjects, zolpidem-MR showed no residual functional impairment in psychometric or cognitive tests sensitive to flurazepam.     

The COX-2 selective inhibitor,valdecoxib, does not impair platelet function in the elderly: results of a randomized controlled trial

The effects of the new cyclooxygenase (COX)-2 selective inhibitor, valdecoxib (40 mg bid; n = 17), on platelet function were evaluated, along with ibuprofen (800 mg tid; n = 15) and placebo (n = 15), in healthy elderly subjects (65-85 years) in this 7.5-day, randomized, single-center, double-blind study. Platelet aggregation (to sodium arachidonate, collagen, and adenosine diphosphate), bleeding time, and serum thromboxane B2 (TxB2) concentrations were measured up to 8 hours postdose on Days 1 and 8. Valdecoxib had no platelet effects, while ibuprofen significantly decreased platelet aggregation, significantly increased bleeding time (2-4 h postdose on each day), and significantly decreased TxB2 levels at all time points. In conclusion, unlike ibuprofen, valdecoxib 40 mg bid spares platelet COX-1 function in healthy elderly subjects. Valdecoxib's lack of effect on platelet aggregation and bleeding time suggests that it will have an improved clinical profile over nonselective NSAIDs, particularly in patients for whom bleeding complications are a concern.     

Effects of single and repeated doses of theophylline on aspects of performance,electrophysiology and subjective assessments in healthy human subjects

The effects of both single and repeated doses of theophylline were evaluated on a battery of nine performance tests, the EEG, the EMG and on subjective assessments of mood and side-effects. The subjects were 20 healthy adults who participated in both phases of this randomized, double-blind, placebo controlled, crossover study. The single dose of 400 mg and the repeated doses of 300 mg b.d. for 4 weeks were intended to attain therapeutic serum concentrations. The Sternberg Additive Factors Method for assessing information processing revealed enhanced performance in both phases of this study, while the Horizontal Addition Test showed improved performance in the single dose phase only. The remaining seven performance tests failed to show significant differences between theophylline and placebo. Single doses of theophylline did not significantly alter mood, but marked adverse effects were encountered in the repeated dose phase, possibly related to unpleasant side-effects. Both EEG and EMG findings indicative of stimulation were associated with a single dose of theophylline, but substantial tolerance developed during 4 weeks of therapy. These findings demonstrate CNS stimulation by both single and repeated doses of theophylline with the occurrence of adverse side-effects during repeated administrations.     

Effects of ethanol and temazepam on performance in memory and psychomotor tasks: a dose-response comparison

In order to compare the effects of ethanol and a benzodiazepine on psychomotor performance and memory, 15 subjects (nine male, six female) aged 20–27 years took part in a five-period crossover study in which they received by mouth in randomised order: (1) ethanol 0·88 g/kg, maximum 66 g for males, 55 g for females; (2) ethanol, 0·75 of condition 1; (3) temazepam 20 mg; (4) temazepam 15 mg; (5) placebo. Both drugs led to significant subjective drunkenness and drowsiness; drunkenness was more marked for ethanol, drowsiness for temazepam. Psychomotor slowing in Digit/Symbol substitution tasks was similar for the two drugs. In the Four-Choice Reaction-Time Task, subjects on ethanol tended to respond faster during the sections of the task where a repetitive sequence of stimuli was given, while those on temazepam slowed down. In the sections with random stimulus sequences, both drugs led to slowing. Ethanol, but not temazepam, led to increased errors in this task. The effect of ethanol on long-term memory in the Buschke selective reminding task was very marked. The trend for temazepam was in the same direction, but not statistically significant. All performance effects were dose-dependent, except the speeding on the Four-Choice task, where the two doses of ethanol had similar effects. These results show that dissociations occur between ethanol and temazepam, ethanol producing more errors at a similar degree of slowing of performance. The effects of ethanol on memory are particularly marked relative to its sedative effect. © 1998 John Wiley & Sons, Ltd.     

Effects of terfenadine and diphenhydramine alone or in combination with diazepam or alcohol on psychomotor performance and subjective feelings

Summary The effects of single oral doses of terfenadine, diphenhydramine and placebo, alone or in combination with diazepam or alcohol, on psychomotor performance and subjective feelings were evaluated in a double-blind, crossover study in 20 normal male volunteers. Terfenadine 60, 120 and 240 mg had no effect on psychomotor skills and subjective feelings, whereas diphenhydramine 100 mg slightly impaired certain features of psychomotor performance and severely worsened subjective feelings. Terfenadine 120 mg did not influence the adverse effects of oral diazepam 10 mg or of alcohol 0.75 g/kg on psychomotor performance and subjective feelings. In contrast, diphenhydramine 100 mg significantly enhanced these effects of diazepam and alcohol.     

Evaluation of the efficacy of metaclazepam and its effects on sleep,psychomotor performance and cognitive function in anxious patients

The effects of single and multiple doses of metaclazepam were investigated in 60 anxious patients. A 15 mg nocturnal dose of metaclazepam was compared to two daily doses (5 mg in the morning and 10 mg at bedtime) in terms of efficacy and effects on various aspects of sleep, cognitive function and psychomotor performance. Anxiolytic efficacy was assessed by means of questionnaires, including the Self Rating Anxiety Scale of Zung, State Trait Anxiety Inventory of Spielberger, and a modified version of the Hamilton Anxiety Rating Scale. Hypnotic activity was evaluated using a clinical rating of insomnia questionnaire. The psychometric battery consisted of tests of Critical Flicker Fusion, Choice Reaction Time and Digit Span. In terms of clinical efficacy, metaclazepam administered in either dosage regimen demonstrated a good anxiolytic activity profile. Both dosage regimens were effective in improving the quality and quantity of sleep, however the number of intermittent awakenings were significantly higher with the daily divided dose. In addition, the nocturnal administration of metaclazepam did not appear to be associated with any undesirable side effects or decrements in psychomotor performance the following morning. In conclusion, it appears that a 15 mg bedtime dose of metaclazepam is efficacious in relieving anxiety without impairing psychomotor performance the following morning. © 1998 John Wiley & Sons, Ltd.