Psychopharmacological effects of vinpocetine in normal healthy volunteers

Summary Twelve healthy female volunteers received pre-treatments with vinpocetine 10, 20, 40 mg and placebo (t.d.s.) for two days according to a randomised, double-blind crossover design. On the third day of treatment and 1 h following morning dosage, subjects completed a battery of psychological tests including Ciritcal Flicker Fusion (CFF), Choice Reaction Time (CRT), Subjective Ratings of Drug Effects (LARS) and a Sternberg Memory Scanning Test. No statistically significant changes from placebo were observed on CFF, CRT or subjective ratings of drug effects. However, memory as assessed using the Sternberg technique was found to be significantly improved following treatment with vinpocetine 40 mg when compared to placebo and results suggested a localised effect of the drug on the serial comparison stage of the reaction process.     

Comparative study of the psychomotor and antistress effects of ritanserin, alprazolam and diazepam in healthy subjects: some trait anxiety-independent responses.

The new potential anxiolytic ritanserin was studied in a double-blind manner vs. alprazolam, diazepam and placebo in 23 healthy subjects. The subjects belonged either to a high anxiety level group or a low anxiety level group, in order to study the effect of the anxiety level on the pharmacodynamic responses. The assessments included cognitive function (memory tests), psychomotor performance [Critical Flicker Fusion (CFF), Choice Reaction Time (CRT)], subjective ratings of alertness and overnight sleep and stress paradigm. Ritanserin (10 mg), alprazolam (0.75 mg), diazepam (10 mg) and placebo were given as single oral doses following a latin square design. Groups were well contrasted on the Cattell anxiety scale and were not overlapping. On no psychometric variable have there been any interactions between the anxiety level and the drug factor. At baseline an anxiety-related difference between the two groups was observed: lower CFF value in the high anxiety group (-1.4 Hz). Both benzodiazepines impaired psychomotor assessment and memory function and increased sleepiness. Ritanserin decreased CFF values without significantly affecting CRT on which nevertheless a trend to impairment was observed. Memory tests, and subjective ratings of alertness were unaffected by ritanserin. A trend to an antistress effect was observed on electrodermogram after ritanserin. Both benzodiazepines decreased central nervous system arousal and memory while ritanserin was inactive except on CFF. Recent data support the hypothesis that 5-HT2 blockers decrease pupil diameter which is a well known covariate of flicker frequency.     

An investigation into the effects of cetirizine on cognitive function and psychomotor performance in healthy volunteers

OBJECTIVE: The cognitive and psychomotor effects of 2.5, 5 and 10 mg cetirizine, a second-generation H1 receptor antagonist, were compared with loratadine 10, 20 and 40 mg, promethazine 25 mg and placebo in 24 healthy volunteers in a double-blind, randomised cross-over study. METHODS: Following each dose, subjects were required to perform a series of tests of cognitive function and psychomotor performance at 1.5, 3 and 6 h post-dose. The test battery consisted of critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking task (CTT) and assessment of subjective sedation (LARS). RESULTS: Cetirizine and loratadine at all doses tested were not significantly different from placebo in any of the tests used. However, as expected for a verum, all measures with the exception of CTT were significantly disrupted by promethazine (P < 0.05). Promethazine caused a reduction in CFF threshold at all test points; these differences were significant at 3 h and 6 h post-dose (P < 0.05). There was also a significant increase in total reaction time at 3 h post-promethazine administration. Subjective reports of sedation were significantly greater following the administration of promethazine at all time points (P < 0.05). CONCLUSIONS: These results allow the conclusion that cetirizine at its recommended therapeutic dose of 10 mg is demonstrably free from disruptive effects on aspects of psychomotor and cognitive function in a study where the psychometric assessments have been shown to be sensitive to impairment, as evidenced by the effects of the positive control, promethazine 25 mg.     

The effects of cigarette smoking on overnight performance

Fifteen healthy smokers and 15 non-smokers were enrolled into this study investigating the effects of smoking on overnight performance. Subjects arrived at the test centre at 1930 hours and were assessed at baseline (2000 hours) and at 2200, 0000, 0200, 0400, 0600, and 0800 hours on a battery of tests (including Critical Flicker Fusion, CFF; Choice Reaction Time, CRT; Compensatory Tracking Task, CTT; Short Term Memory Task, STM; and the Line Analogue Rating Scale, LARS). Results showed that the performance of the smokers was more consistent with baseline measures than that of the non-smokers, which became more impaired throughout the night on a number of tasks [CFF (P < 0.005), Total Reaction Time (TRT, P < 0.05), CTT (P < 0.05) and the Reaction Time (RT) aspect of the CTT task (P < 0.0005)]. The Recognition Reaction Time (RRT) aspect of the CRT task showed that the performance of the non-smokers became more impaired from baseline (P < 0.005), while that of the smokers remained at baseline levels until 0400 hours, when it deteriorated to become comparable to that of the non-smoking controls. Subjective sedation ratings (LARS) resulted in comparable levels of impairment for both study groups (P < 0.00005). Findings from the STM task failed to reach significance. These data suggest that when performance is being measured overnight, smokers show little or no impairment, whilst the performance of non-smokers showed performance decrements. Received: 29 May 1997/Final version: 22 September 1997     

Pharmacodynamics of milnacipran in young and elderly volunteers

AIMS: To investigate the pharmacodynamics of milnacipran in healthy young and elderly volunteers. METHODS: Randomized double-blind crossover designs were employed and a standardized psychometric battery was administered pre and post dose for both studies. In the first study 10 healthy young volunteers received milnacipran 12.5 mg, 25 mg, 50 mg, 100 mg as a single dose or matched placebo. The test battery was administered at baseline and at 1, 2, 4 and 6 h post dose. The second study compared the effects of milnacipran 75 mg (50 mg+25 mg) per day, amitriptyline 50 mg (25 mg+25 mg) per day and placebo for 3 days' dosing in healthy volunteers aged over 65 years. The test battery was administered at baseline and at 2, 10 and 24 h post dose. The psychometric battery included critical flicker fusion (CFF), choice reaction time (CRT), compensatory tracking (CTT) and tests of short-term memory (STM), subjective sedation (LARS) and subjective sleep (LSEQ). RESULTS: Milnacipran produced no significant dose related effects in the young volunteers. For the elderly, milnacipran significantly (P<0.05) raised CFF scores compared with placebo but had no significant effects on any of the other measures used. Amitriptyline, in contrast, significantly (P<0. 05) lowered CFF threshold, lengthened CRT and increased error on the CTT. On the subjective variables, LARS and LSEQ, amitriptyline increased ratings both of sedation and of difficulty in waking from sleep. CONCLUSIONS: The results showed that milnacipran at single doses of up to 100 mg in healthy young volunteers is free from disruptive effects on cognitive function and psychomotor performance. In addition, milnacipran 75 mg (50+25 mg) appears to be free of negative effects on cognitive function in elderly volunteers, where it seemingly improves performance on CFF. In contrast, the tricyclic antidepressant amitriptyline, used here as a positive internal control, significantly impaired performance in the elderly on the majority of psychometric measures used in this study. This finding not only validated the sensitivity of this current test battery but also indicates the potential behavioural toxicity of amitriptyline in clinical use in the elderly.     

Effects of tianeptine and mianserin on car driving skills

RATIONALE: Tianeptine is a novel antidepressant which enhances the reuptake of serotonin (5-HT). Previous studies suggest that tianeptine has a non-sedative side-effect profile, but its effects on everyday activities including car driving have not been fully explored. OBJECTIVES: To assess the effects of tianeptine on tests related to car driving performance. METHOD: Sixteen healthy volunteers received acute doses of tianeptine 12.5 mg and 37.5 mg, mianserin 30 mg and placebo in a double blind four-way crossover study. The effects of treatment on self assessed ratings of sedation (LARS), two valid and reliable laboratory performance measures, critical flicker fusion (CFF) and choice reaction time (CRT) and an "on-the-road" measure of one aspect of car driving performance, brake reaction time (BRT) were examined. The BRT test was administered at baseline and at 1.5, 3, 4.5 and 6 h post-dose, while LARS, CFF and CRT were administered at baseline and at 1, 2, 4 and 5 h post-dose. For all data, the maximum change from baseline was calculated and used in the analysis. RESULTS: Tianeptine had no measurable effect on performance, compared to placebo, on any of the variables investigated. Compared to placebo, mianserin was shown to lower CFF thresholds (P = 0.01), increase reaction times on both the CRT (P = 0.001) and the BRT (P = 0.01) tests and was subjectively rated as more sedative than placebo (P = 0.01). CONCLUSION: The apparent lack of counter-therapeutic side-effects produced by an acute dose of tianeptine suggest that it may be a suitable antidepressant for use in an ambulant population.     

Evaluation of cognitive and psychomotor effects of nisoldipine or placebo in healthy volunteers

The purpose of this study was to compare the cognitive and psychomotor effects of the calcium antagonist nisoldipine with placebo in healthy volunteers over the three-week period of this randomised, double-blind, parallel group trial. Thirty volunteers received either a twice-daily dose of 10 mg nisoldipine or placebo. Psychometric testing and measurement of blood pressure and heart rate were carried out on days 0, 7, 14 and 21. Psychometric testing included: Critical Flicker Fusion (CFF), Choice Reaction Time (CRT), Digit Span (DS), Digit Symbol Substitution Test (DSST), and Letter Cancellation (LC). No significant treatment effects were found. CFF performance improved for both groups during the first week. In the CRT task, significant improvements were observed on days 14 and 21, relative to baseline, for total and motor reaction time. Similar improvements over time were found on the LC and DSST tasks. There were no significant differences between the active treatment and placebo for heart rate and systolic/diastolic blood pressure and nisoldipine was well tolerated. The results of this study indicate that nisoldipine does not have any cognition enhancing properties but, unlike some calcium antagonists, it does not markedly impair CNS activity. Copyright 2000 John Wiley & Sons, Ltd.     

The effects of paroxetine and other antidepressants in combination with alcohol in psychomotor activity related to car driving

Ten healthy female volunteers received single doses of amitriptyline 50 mg (AMI); mianserin 20 mg (MIA); trazodone 50 mg (TRA); paroxetine 30 mg (PAR) and placebo (PLA), with or without a ‘social’ dose of alcohol (ALC) in a double-blind, balanced crossover study where each subject acted as her own control. Psychomotor activity related to car handling ability was measured on a battery of tests at 1.5 and 4 h following study drug. The tests included tracking accuracy (RMS) and latency of response to a peripheral stimulus (RT) as measures of sensorimotor co-ordination; the Maddox Wing test (MW) for the balance of extraocular muscles; critical flicker fusion threshold (CFF) for overall levels of CNS activity; choice reaction time (CRT) for psychomotor performance and the latency of brake reaction time (BRT) measured in a driving simulator. Subjective ratings of sedation were measured on line analogue ratings scales (VARS) and the Leeds Sleep Evaluation Questionnaire (LSEQ). When compared to PLA on objective tests, AMI significantly impaired RMS, RT, MW and CFF at 4 h post-drug and AMI + ALC similarly impaired the same measures and BRT. MIA produced a significant impairment of RT, MW, CFF and CRT at both 1.5 and 4 h. MIA + ALC further impaired RMS at 1.5 and 4 h and BRT at 4 h. TRA showed a detrimental activity on CFF at 1.5 h and CFF, RT, MW and BRT at 4 h. TRA + ALC produced a greater effect than TRA alone at 1.5 h and significantly impaired RT, MW, TRT, BRT. There were no significant effects of TRA + ALC at 4 h. PAR alone had no measurable effect on any of the test measures at either 1.5 or 4 h after treatment. PAR + ALC impaired RT at 1.5 and 4 h but had no effect on any other measures at either test times. Indeed, compared to PLA, CFF levels were significantly improved at 4 h following both PAR and PAR + ALC and improvements in RRT were also measured 4 h after taking PAR. Subjective measures (VARS) compared to placebo, show AMI at 4 h and AMI + ALC at 1.5 and 4 h, both MIA and MIA + ALC after 1.5 and 4 h, TRA + ALC after 1.5 h and PAR + ALC at 4 h to have significant sedative activity. In this placebo-controlled study, acute doses of AMI 50 mg, MIA 20 mg and TRA 50 mg alone and with alcohol showed evidence both of significant impairment of psychomotor skills related to vehicle handling and of perceived sedation at 1.5 and / or 4 h following treatment. Under identical circumstances PAR 30 mg produced no detrimental effect on any of the test measures, there was an impairment with PAR + ALC of one component of a divided attention task and on a subjective measurement of sedation.     

A comparison of the psychometric effects of remoxipride with those of haloperidol,thioridazine, and lorazepam in healthy volunteers

In this placebo and verum (lorazepam 2 mg) controlled double-blind crossover study the acute effects of Remoxipride 50 mg and 100 mg; Haloperidol 2·5 mg; and Thioridazine 50 mg were examined in 18 healthy volunteers. CNS function was assessed using a battery of psychometric measures, viz: Critical Flicker Fusion Threshold (CFFT); Choice Reaction Time (CRT); Tracking Accuracy (RMS) and Peripheral Reaction Time (PRT); Sternberg Memory Scanning (SMS); Word Memory (WM) as well as Line Analogue Ratings of subjective sedation (LARS) and the Leeds Sleep Evaluation Questionnaire (LSEQ). Both doses of remoxipride were associated with a reduction of CFFT: 0·9 Hz for 50 mg and 1·3 Hz for 100 mg. The 100 mg dose caused an increase (impairment) in CRT total time of 38 msec. Haloperidol reduced CFFT, while thioridazine and lorazepam impaired performance on the majority of objective measures, as expected for known sedative drugs. Thioridazine led to hypotension in three subjects, and to subjective sedation (LARS), but no treatment affected responses on the LSEQ administered the morning of the day following treatment. These results show that remoxipride has some depressant effects on CNS function, but that these are less prominent than those of sedative neuroleptics such as thioridazine.     

The acute and sub-chronic effects of levocetirizine, cetirizine, loratadine, promethazine and placebo on cognitive function, psychomotor performance, and weal and flare

AIM: To compare the central and peripheral H1 inhibitory effects of acute and sub-chronic doses of levocetirizine (L-CTZ), cetirizine (CTZ), loratadine (LOR) and promethazine (PRM) versus placebo, using a battery of psychomotor and cognitive tests together with measures of the weal and flare reaction. PRM was included in the study as a positive internal control to validate the sensitivity of the psychometric test battery to the CNS effects of the various treatments. METHODS: Twenty healthy volunteers (18-50 years) received L-CTZ 5mg, CTZ 10 mg, LOR 10 mg, PRM 30 mg and placebo once daily for four days in a five-way, double-blind, crossover study. For each treatment condition, subjects were assessed using a psychometric test system and a pinprick weal and flare response to 100 mg/ml histamine solution at baseline and at 1, 2, 3 ,4, 6, 8, 10 and 122 hours post-dose on days 1 and 4. The psychometrics comprised critical flicker fusion (CFF), choice reaction time (CRT), a continuous tracking task (CTT) and subjective rating scales for sedation (LARS). On days 2 and 3, subjects took their medication at pre-designated times while out of the unit. RESULTS: The verum (PRM) established the sensitivity of the test battery: a significant overall reduction in CFF thresholds on both days 1 and 4 (p < 0.05); an overall significant increase (impairment) in recognition, motor and total reaction times on day 1 (p < 0.05); a significant impairment of both the tracking accuracy and reaction time aspects of the CTT task on day 1 (p < 0.005) and significantly higher ratings of subjective sedation on day 1 (p < 0.05). L-CTZ, CTZ and LOR were not distinguishable from placebo in any of the objective and subjective tests at any time point on either day 1 or day 4. With regards to the peripheral inhibitory effects, L-CTZ inhibited both the weal and flare reaction, with maximum inhibition (almost 100%) occurring within two hours of drug ingestion. CTZ also showed evidence of potent peripheral inhibition of histamine, whereas PRM, and especially LOR, showed only a weak weal and flare reaction which had completely attenuated at day 4. CONCLUSIONS: In a study where the psychometric assessments were shown to be sensitive to impairment, L-CTZ 5 mg was found following both initial and repeated doses, but also to be demonstrably free from disruptive and sedative effects on objective measures of psychomotor and cognitive function. Similarly, CTZ showed evidence of pronounced antihistaminic activity and significantly reduced weal and flare scores after both acute and repeated doses, again without evidence of cognitive or psychomotor impairment. LOR also was non-sedative but the antihistaminic reaction was demonstrably weak.     

A preliminary investigation of “albert 285” (HWA 285) on psychomotor performance,mood, and memory

Eight healthy female volunteers received 150, 300, and 450 mg of HWA 285 and placebo according to a randomized, double-blind crossover design. The subjects completed a battery of psychological tests including critical flicker fusion (CFF), choice reaction time (CRT), subjective ratings of drug effects (LARS), and a Sternberg memory scanning test (SMST) 1 and 2 hr following treatment. No statistically significant changes from placebo were observed on CFF, CRT, or subjective ratings of drug effects. However, memory as assessed using the Sternberg technique was significantly improved with respect to placebo 1 hr following treatment with HWA 285 at 150, 300, and 450 mg dose levels. The action of the drug was found to be specific in its effects on the central serial comparison stage of the information processing model.     

The psychopharmacological effects of Ginkgo biloba extract in normal healthy volunteers

Eight healthy female volunteers received Ginkgo biloba extract (G.B.E.) 120, 240, 600 mg and placebo according to a randomized, double-blind crossover design. One hour following treatment, subjects completed a battery of psychological tests including critical flicker fusion (CFF), choice reaction time (CRT), subjective ratings of drug effects (LARS) and a Sternberg memory scanning test. No statistically significant changes from placebo were observed on CFF, CRT or subjective ratings of drug effects. However, memory as assessed using the Sternberg technique was found to be significantly improved following treatment with G.B.E. 600 mg when compared to placebo and results suggested a localized effect of the drug on the serial comparison stage of the reaction process.     

The effects of acute doses of dothiepin (25, 50, and 75 mg) versus placebo on psychomotor performance and cognitive function

Sixteen healthy volunteers received dothiepin 25 mg, 50 mg, 75 mg and placebo in a double-blind crossover study. Each subject received the four treatments once, with a 6-day washout period between test days. On each occasion psychomotor performance and cognitive function were measured 30 min before dosing and 1, 2, 4, 6 and 8 h after drug administration. The test battery comprised: Critical Flicker Fusion, Choice Reaction Time, Continuous Tracking and Short Term Memory. Subjective ratings of sedation were measured using Line Analogue Rating Scales. Dothiepin at the subtherapeutic dose of 75 mg was shown to produce statistically significant impairment (p<0·05) on several of the variables investigated. These included CFF at the 2- and 4-h test points, TRT at the 2-h test point and LARS at the 2- and 4-h test points. Lower doses also produced impairment of cognitive function and psychomotor performance as measured by the present test battery. © 1997 John Wiley & Sons, Ltd.     

Alprazolam and lorazepam single and multiple-dose effects on psychomotor skills and sleep

Summary The effects of alprazolam 0.5 mg and lorazepam 2 mg on cognitive and psychomotor skills were assessed in twelve normal volunteer subjects in a randomised, double-blind, crossover design. Single and multiple dose effects were monitored using a battery of tests comprising critical flicker fusion threshold (CFFT), choice reaction time (CRT), simulated car tracking, and subjective ratings of perceived sedation (LARS) and of sleep behaviour (LSEQ). Compared with placebo baseline scores, treatment with lorazepam 2 mg (both single and multiple doses) resulted in a widespread impairment of CRT, tracking accuracy, and CFFT. Single doses of alprazolam 0.5 mg reduced CFFT with respect to the placebo baseline. Single and multiple dose treatment with both drugs resulted in subjective reports of sedation, a reduction of sleep onset latency, and improved sleep quality. Only lorazepam 2 mg significantly disrupted the integrity of behaviour on waking from sleep. These results suggest important pharmacodynamic differences between the two drugs in the doses used.     

Effects of clobazam and clonazepam on saccadic eye movements and other parameters of psychomotor performance

Summary The effects of two benzodiazepine anti-convulsants clobazam (20 mg) and clonazepam (2 mg) in a variety of psychomotor performance tests were compared in a placebo controlled double-blind acute oral dose study in ten healthy volunteers. Assessments included critical flicker fusion (CFF) threshold, the Sternberg memory scanning and choice reaction time (CRT), peak saccadic velocity (PSV) and visual analogue scales, all previously shown to be sensitive to the effects of benzodiazepines.Clobazam did not significantly impair saccadic eye movements, CFF threshold, Sternberg memory scanning and CRT compared to placebo. Clonazepam significantly lowered PSV, reduced the CFF threshold, slowed the Sternberg CRT and decreased an alertness factor in the visual analogue scales compared to placebo. Clonazepam significantly increased memory scanning time compared to clobazam. Clobazam was remarkably free of cognitive and psychomotor side-effects.     

A double-blind, placebo-controlled investigation of the effects of fexofenadine, loratadine and promethazine on cognitive and psychomotor function

AIMS: To assess whether fexofenadine in a range of doses from 80 to 180 mg has any disruptive effects on aspects of psychomotor and cognitive function in comparison with placebo, loratadine and promethazine, an antihistamine known to produce psychomotor and cognitive impairment. METHODS: Twenty-four healthy volunteers received fexofenadine 80 mg, 120 mg and 180 mg, loratadine 10 mg, promethazine 30 mg (as a positive internal control) and placebo in a six-way crossover, double-blind study. Following each dose, subjects were required to perform a series of tests of cognitive function and psychomotor performance at 1.5, 3, 6, 9, 12 and 24 h post dose. The test battery included critical flicker fusion (CFF), choice reaction time (CRT) and assessment of subjective sedation (LARS). Overall levels of activity were monitored by means of wrist mounted actigraphs throughout each of the 24 h experimental periods. RESULTS: Fexofenadine at all doses tested was not statistically different from placebo in any of the tests used and loratadine did not cause any significant impairment of cognitive function. Significant impairments were found following promethazine. Promethazine caused a significant reduction in CFF threshold and this effect was evident up to 12 h post dose (P<0.05). There was a significant increase in recognition reaction time at 3 and 6 h post promethazine administration, and the drug caused a significant (P<0. 002) increase in the percentage of 'sleep-like' activity from actigraph records during the daytime. CONCLUSIONS: Fexofenadine at doses up to 180 mg appears free from disruptive effects on aspects of psychomotor and cognitive function in a study where the psychometric assessments have been shown to be sensitive to impairment, as evidenced by the effects of the verum control promethazine 30 mg.     

The Acute and Sub-chronic Effects of Levocetirizine,Cetirizine, Loratadine,Promethazine and Placebo on Cognitive Function,Psychomotor Performance,and Weal and Flare

Summary

Aim: To compare the central and peripheral H1 inhibitory effects of acute and sub-chronic doses of levocetirizine (l-CTZ), cetirizine (CTZ), loratadine (LOR) and promethazine (PRM) versus placebo, using a battery of psychomotor and cognitive tests together with measures of the weal and flare reaction. PRM was included in the study as a positive internal control to validate the sensitivity of the psychometric test battery to the CNS effects of the various treatments.

Methods: Twenty healthy volunteers (18–50 years) received l-CTZ 5?mg, CTZ 10?mg, LOR 10?mg, PRM 30?mg and placebo once daily for four days in a five-way, double-blind, crossover study. For each treatment condition, subjects were assessed using a psychometric test system and a pinprick weal and flare response to 100mg/ml histamine solution at baseline and at 1, 2, 3,4, 6,8,10 and 12?hours post-dose on days 1 and 4. The psychometrics comprised critical flicker fusion (CFF), choice reaction time (CRT), a continuous tracking task (CTT) and subjective rating scales for sedation (LARS). On days 2 and 3, subjects took their medication at pre-designated times while out of the unit.

Results: The verum (PRM) established the sensitivity of the test battery: a significant overall reduction in CFF thresholds on both days 1 and 4 (p?<?0.05); an overall significant increase (impairment) in recognition, motor and total reaction times on day 1 (p?<?0.05); a significant impairment of both the tracking accuracy and reaction time aspects of the CTT task on day 1 (p?<?0.005) and significantly higher ratings of subjective sedation on day 1 (p?<?0.05). l-CTZ, CTZ and LOR were not distinguishable from placebo in any of the objective and subjective tests at any time point on either day 1 or day 4. With regards to the peripheral inhibitory effects, l-CTZ inhibited both the weal and flare reaction, with maximum inhibition (almost 100%) occurring within two hours of drug ingestion. CTZ also showed evidence of potent peripheral inhibition of histamine, whereas PRM, and especially LOR, showed only a weak weal and flare reaction which had completely attenuated at day 4.

Conclusions: In a study where the psychometric assessments were shown to be sensitive to impairment, l-CTZ 5?mg was found not only to be a potent inhibitor of the histamine-induced weal and flare reaction,     

The Effects of Cigarette Smoking on Late Night Performance

This study was undertaken in order to determine the effects of an occasional late night on both smokers and non-smokers. Sixteen smokers and 16 non-smokers aged 24–45 years were enrolled onto the study. Full test batteries (comprising of Critical Flicker Fusion, CFF; Choice Reaction Time, CRT; Sternberg Short-Term Memory Task, STM; Compensatory Tracking Task, CTT; and Line Analogue Rating Scales, LARS) were completed at 18.00 h, 22.00 h, 00.00 h, 02.00 h and 08.15 h in the morning. Subjects were put to bed at 02.30 h and awakened at 07.55 h. Smokers were permitted to smoke freely throughout the trial period. CFF thresholds for the smokers remained almost constant throughout the evening, whilst those from the non-smoking control group dropped significantly from baseline (p < 0·0001). The CRT test showed that for both RRT and TRT performance remained almost constant for the non-smoking group compared with baseline, whilst the smokers' RRT improved significantly (p < 0·05) over time. TRT was quicker throughout for the smokers relative to baseline, but this did not reach significance. Performance on the MRT component was significantly quicker than baseline for the smokers at 22.00 h and 02.00 h. The RT element of the CTT task was impaired throughout the night for both groups but performance was notably better for the smoking group. Tracking error was comparable. STM gradually improved from baseline in both groups, to a greater extent in the smokers. There was a significant effect of time from the LARS data (p < 0·001) as both groups followed the pattern of the other with regards to subjective tiredness, alertness and drowsiness. When people are required to perform tasks in the late night and early morning smokers show no decrement, whilst the performance of non-smokers gets worse. © 1997 John Wiley & Sons, Ltd.     

Separate and combined effects of the social drugs on psychomotor performance

Ten female subjects (five smokers and five non-smokers) performed a choice reaction time task (CRT), a compensatory tracking task (CTT), a short-term memory task (STM) and were tested for their critical flicker fusion threshold (CFF) at set points over 4 h after the administration of each possible combination of nicotine (2 mg gum or placebo), caffeine (250 mg capsule or placebo) and alcohol (30 g or placebo). Memory and motor function were shown to be facilitated by nicotine or caffeine, and the debilitating effects of alcohol were frequently antagonised by either drug. In spite of the differences in their neuropharmacological actions, combinations of nicotine, caffeine and alcohol may be compared through their effects on common information processing mechanisms involved in psychomotor performance.     

Assessment of the interaction between a partial agonist and a full agonist of benzodiazepine receptors, based on psychomotor performance and memory, in healthy volunteers

Potential interactions between the imidazopyridine anxiolytic alpidem and the full benzodiazepine agonist lorazepam were assessed in a randomized, double-blind, four-way cross-over, placebo-controlled study in 16 healthy young male volunteers. Each volunteer received alpidem, 50 mg, or a placebo twice daily for 8 days with a 1- week wash-out interval. The interaction between alpidem, at the steady state, and a single oral dose of lorazepam 2 mg or a placebo was assessed after concomitant administration on days 7 or 9 of each treatment period. Psycho motor performance and cognitive function were evaluated before and 2, 4, 6 and 8 h post-dose, using objective tests [critical flicker fusion threshold (CFF), choice reaction time (CRT), digit-symbol substitution (DSST), body sway and short-term memory (Sternberg memory scanning)] and self-ratings [line analogue rating scales: (LARS)]. Long-term memory (delayed free recall and recognition of pictures) was assessed before the dose and 2 and 4 h post-dose. Pharmacodynamic interactions were evaluated by applying repeated measures ANOVA to a 2 x 2 factorial interaction model. Alpidem, 50 mg twice daily at the steady state, was free of any clinically relevant detrimental effects on skilled performance, information processing or memory. In contrast, a single 2 mg dose of lorazepam induced marked impairment of psychomotor performance and cognitive function (significant reductions in CFF and DSST and increases in CRT and body sway), as well as subjective sedation from 2 to 8 h post-dose, depending on the test used. In addition, lorazepam induced anterograde amnesia, characterized by a decrease in delayed free recall and recognition, and a deficit in short-term memory. Finally, alpidem 50 mg did not potentiate the detrimental effects of lorazepam 2 mg. On the contrary, alpidem significantly antagonized the lorazepam-induced CRT increase and anterograde amnesia, and produced similar trends on most of the other cognitive parameters; thus, the results obtained with the combination of alpidem and lorazepam consistently indicated less impairment than those measured after lorazepam alone. These results are consistent with the suggested partial agonsist properties of alpidem at the benzodiazepine receptor and indicate that such properties can be assessed in humans based on antagonism of the effects of a full agonist.