The effects of reboxetine on autonomic and cognitive functions in healthy volunteers

RATIONALE: Though reboxetine, a selective noradrenaline reuptake inhibitor, causes autonomic and cognitive adverse events there is a paucity of appropriately designed studies on the cognitive and autonomic effects of the drug in the literature. OBJECTIVE: To compare the effects of reboxetine on cognitive and autonomic functions with those of placebo in healthy humans. METHOD: A randomised, double-blind, crossover study of 12 healthy male volunteers aged 25 (21-27; median, range) years. Subjects orally received 4 mg reboxetine and placebo twice daily for periods of 14 days each with at least 14 days in between. Vasoconstrictory response of cutaneous vessels (VR) and skin conductance response (SCR) following sudden deep breath were employed as parameters for autonomic function. Quantitative EEG (qEEG) and psychometric tests served as parameters for cognitive function. RESULTS: Reboxetine decreased SCR and prolonged the dilation phase of VR (P<0.05). It did not affect cognitive functions such as flicker fusion frequency, choice reaction, memory and psychomotor coordination but increased slow beta (beta1) power density in the qEEG. Tiredness (n=12), dry mouth (n=9), delayed urination (n=3) and constipation (n=1) were noted with reboxetine. CONCLUSION: Sustained peripheral and/or central sympathetic activation accounts for the prolongation of VR. The decrease of SCR and typical side effects suggest a relevant antimuscarinic drug action. Chronic administration of reboxetine at therapeutic doses causes autonomic dysfunction and subjective sedation but does not impair cognitive and psychomotor abilities in healthy humans.     

The effects of St John's wort extract on heart rate variability,cognitive function and quantitative EEG: a comparison with amitriptyline and placebo in healthy men

AIMS: To compare the effects of multiple dosing with St John's wort (Hypericum perforatum) extract and amitriptyline on heart rate variability, cognitive function and quantitative EEG (qEEG) with placebo in healthy humans. METHODS: A randomized, double-blind, cross over study of 12 healthy male volunteers. Subjects orally received capsules with 255-285 mg St John's wort extract (900 micro g hypericin content), 25 mg amitriptyline and placebo three times daily for periods of 14 days each with at least 14 days between. The doses of amitriptyline and St John's wort extract are comparable with respect to their antidepressant activity. Compliance was confirmed by coadministration of 10 mg of riboflavin with each capsule and detection of urinary vitamin B2 on treatment day 11 with high performance liquid chromatography. Measurements of heart rate variability, psychometric tests and qEEG were performed before start of medication and repeatedly on the last treatment day. RESULTS: St John's wort extract did not affect heart rate variability (HRV) whereas amitripytline significantly decreased it: the difference in the percentage number of adjacent RR intervals> 50 ms (pNN50) was 8.6 (-2.6, 19.9; mean; 95% confidence interval) between St John's wort extract and placebo and -17.6 (-24.7, -10.4) between amitriptyline and placebo. Neither St John's wort extract nor amitriptyline had an influence on cognitive performance such as choice reaction, psychomotor coordination, short-term memory and responsiveness to distractive stimuli. Amitriptyline but not St John's wort extract decreased self rated activity (P < 0.05). Both drugs caused significant qEEG changes. St John's wort extract increased theta power density. Amitriptyline increased theta as well as fast alpha power density. CONCLUSIONS: Multiple doses of St John's wort extract do not affect heart rate variability nor cognitive function. Chronic administration of amitriptyline causes a decrement of HRV and subjective sedation but it does not impair cognitive performance.     

Acute autonomic nervous system effects of caffeine in prepubertal boys

The effects of caffeine on autonomic activity were tested in 19 normal prepubertal boys. Subjects received placebo, 3 mg/kg, and 10 mg/kg caffeine in a random order (double blind) before three test sessions 48 h apart. Skin conductance (SC), heart rate (HR), and skin temperature (ST) were recorded during a rest period, a series of nonsignal tones, and a simple reaction time (RT) task. Caffeine increased the frequency of both spontaneous and elicited SC responses (SCR) under all conditions. Resting SC base level (SCL) was increased, and shorter SCR half recovery time also occurred in some periods. In contrast, caffeine decreased HR and motor activity at 3 mg/kg. Evidence of improved attention on caffeine was also obtained. The physiological effects are partially similar to the effects seen in clinical anxiety states, and they are also consistent with the physiological concomitants of good sustained attention. The profile of effects did not resemble those of dextroamphetamine in a similar population.     

Characterization of a psychophysiological model of classical fear conditioning in healthy volunteers: influence of gender,instruction, personality and placebo

Two experiments are described which evaluate the role of associative mechanisms and placebo effects on aversively conditioned skin conductance responses in groups of healthy volunteers. In both experiments, skin conductance level (SCL), variability (spontaneous fluctuations, SF) and amplitude (SCR) were recorded during a sequence of tone stimuli (80 dB, 1 s, 360 Hz). All the variables habituated during the first ten presentations of the tones. Tone 11 was immediately followed by a loud (100 dB) aversive brief (1 s) white noise UCS. The conditioning trial significantly enhanced SCRs to a further ten presentations of the tones and increased SCL and variability (SF). No enhancement of SCRs occurred when tone 11 was omitted and the UCS occurred in temporal isolation (experiment 1). Thus enhanced SCRs to tones following paired tone-noise presentation involves an associative mechanism. Increased "spontaneous" variability was shown to involve both conditioning and sensitization following the UCS. In both experiments females showed greater conditioned SCRs than males. In experiment 2 no effect of "anxiolytic" placebo could be discerned and there were no general relationships between questionnaires scores of extraversion or neuroticism with skin conductance measures in a group of 40 volunteers. The results question the role of conditionability and autonomic lability as major determinants of extraversion and neuroticism. These studies validate the use of the psychophysiological model of aversive conditioning in pharmacological studies of the mechanisms of habituation, conditioning and sensitization.     

Psychopharmacological effects of sertraline in normal, healthy volunteers

Summary A double-blind, placebo controlled, cross-over study was carried out in 10 normal healthy volunteers to investigate the effects of sertraline 25 mg, 50 mg, 75 mg and 100 mg on aspects of cognitive functioning.Changes with respect to placebo in objective tests of psychomotor function (critical flicker fusion and choice reaction time) showed that sertraline had an alerting effect. The changes were not consistent with subjective reports of drowsiness.     

The impact of sertraline,desipramine, and placebo on psychomotor functioning in depression

Impairment of psychomotor performance is a common adverse effect of many antidepressants, particularly tricyclics. Desipramine is thought to be an exception, with possible performance enhancing effects on psychomotor function. This multicentre study examined the relative effects on psychomotor function of sertraline versus desipramine versus placebo in mild to moderate depression. Fifty-eight patients who satisfied DSM-III-R criteria for major depression and had a minimum HAM-D score of 15 (17 items) completed eight weeks of treatment. They underwent a standardized assessment which included depression and anxiety rating scales (HAM-D, HAM-A, MADRS) and a battery of psychomotor performance tests (The Simple and Choice Reaction Time, The Digit Symbol Substitution and The Trail Making Test), before, during, and after eight weeks of treatment with sertraline, desipramine, or placebo. At baseline, there was a trend for both the sertraline and placebo groups to exhibit better psychomotor performance than desipramine. No significant differences were found between groups after treatment nor between groups for the change from baseline to week 8. However, at week 3, the sertraline group performed significantly better in the trail making test than the placebo patients (p<0.05). Within each treatment group, there was a trend towards improvement in performance for all four parameters from baseline to the end of the study, with these improvements being most obvious in the desipramine group. Sertraline, however, was found to be associated with significantly fewer other adverse effects than the desipramine group, i.e. sweating, dry mouth, anorexia. These results suggest that desipramine and sertraline do not adversely affect psychomotor performance and may even enhance it in mild to moderately depressed patients.     

焦虑症患者心率变异性与自主神经功能的相关性研究

目的 探讨焦虑症患者心率变异性与自主神经功能的相关性,为焦虑症患者心身疾病的防治提供理论参考.方法 对90例广泛性焦虑症、惊恐障碍患者和90例健康查体者进行心理问卷测试,并采用汉密顿焦虑量表（HAMA）和汉密顿抑郁量表（HAMD）进行焦虑和抑郁症状的评定,采用24 h动态心电图记录监测心率及心率变异性指标（SDNN、SDANN、RMSSD、PNN50）.结果 焦虑症（GAD）组平均心率显著高于对照组,两组差异均有统计学意义（P〈0.05）;心率变异性各指标均显著低于对照组,两组差异均有统计学意义（P〈0.05）;GAD组的各心率变异性指标均显著低于对照组,而惊恐障碍（PD）组的各心率变异性指标均显著低于GAD组,差异均有统计学意义（P〈0.05）.结论 焦虑症患者存在较高水平的交感神经活动功能,自主神经功能紊乱,且PD患者的交感神经活动功能增高,自主神经功能紊乱程度增加.     

Dose-response evaluation of the interaction between sertraline and alprazolam in vivo

In vitro data show the inhibition of alprazolam metabolism by sertraline via CYP3A4; therefore, using a randomized, double-blind, placebo-controlled design, the authors conducted this study to assess the potential for similar in vivo inhibition in humans. Ten healthy volunteers participated in two test sessions (placebo/alprazolam 1 mg orally) before the initiation of sertraline treatment. Blood samples were obtained over a 32-hour period and pharmacodynamic measures (sedation, psychomotor performance, memory function) were obtained over an 8-hour period. After a minimum of 2 weeks of daily sertraline self-administration (50, 100, or 150 mg/day), test sessions were repeated. Alprazolam concentrations (N = 6, 4, and 6 at sertraline doses of 50, 100, and 150 mg/day, respectively) showed no significant changes based on peak concentration (Cmax), time to maximum concentration (Tmax), elimination half-life (t1/2[beta]), and area under the concentration-time curve (AUC(0-8)), with the exception of a reduced Cmax in the 50 mg/day group. Similarly, dynamic data showed no significant variations based on peak effect, Tmax, and AUC(0-infinity), with the exception of increased peak impairment in one measure of psychomotor performance. No differences were detected between placebo alone and placebo plus sertraline. These findings suggest that sertraline (50-150 mg/day) does not alter the single-dose kinetics or dynamics of alprazolam; therefore, the combination may be prescribed without an increased risk of alprazolam toxicity.     

心率变异性对糖尿病自主神经损伤的评价意义

目的探讨心率变异性(HRV)在糖尿病患者中的应用价值。方法对64例糖尿病患者(糖尿病组)检测24h动态心电图,观察心率变异性(HRV)结果,并与60例健康者(健康对照组)心率变异性(HRV)对照分析。结果两组心率变异性(HRV)下降发生率分别为84.375%、5%,差别具有高度显著性;两组SDNN值(全部正常窦性心搏RR时期的标准差)分别为(107±40)、(136±34)ms;SDANN值(全程记录每5min窦性RR间期平均值的标准差)分别为(87±30)、(112±33)ms,差别均具有高度显著性。结论糖尿病患者自主神经病变是糖尿病最常见的并发症之一,心率变异性(HRV)具有早期诊断和预测糖尿病患者是否伴有自主神经病变的价值。     

Heart-rate variability effects of beta-adrenoceptor agonists (xamoterol, prenalterol, and salbutamol) assessed nonlinearly with scatterplots and sequence methods.

Full antagonists of the cardiac beta-adrenoceptor improve heart-rate variability (HRV) in humans; however, partial agonism at the beta2-adrenoceptor has been suggested to decrease HRV. We therefore studied the HRV effects of some partial agonists of the beta1- and beta2-adrenoceptors in normal volunteers. Under double-blind and randomised conditions (Latin square design), eight healthy volunteers received placebo; xamoterol, 200 mg (beta1-adrenoceptor partial agonist); prenalterol, 50 mg (beta1- and beta2-adrenoceptor partial agonist); salbutamol, 8 mg (beta2-adrenoceptor partial agonist); ICI 118,551, 25 mg (selective beta2-adrenoceptor antagonist); and combinations of each partial agonist with ICI 118,551. Single oral doses of medication (at weekly intervals) were administered at 22:30 h with HRV assessed from the overnight sleeping heart rates. HRV was determined by using standard time-domain summary statistics and two nonlinear methods, the Poincaré plot (scatterplot) and cardiac sequence analysis. On placebo, the sleeping heart rate decreased significantly, between 2 and 8 h after dosing. The heart rate with ICI 118,551 was unaltered. Xamoterol, prenalterol, and salbutamol increased the sleeping heart rate. ICI 118,551 blocked the heart-rate effects of salbutamol, attenuated those of prenalterol, but did not influence the xamoterol heart rate. The scatterplot (Poincaré) area was reduced by beta1-adrenoceptor (xamoterol), beta2-adrenoceptor (salbutamol), and combined beta1- and beta2-adrenoceptor (prenalterol) agonism. A reduction in scatterplot length followed salbutamol, prenalterol alone, and prenalterol in combination with ICI 118,551. The geometric analysis of the scatterplots allowed width assessment (i.e., dispersion) at fixed RR intervals. At higher heart rates (i.e., 25 and 50% of RR scatterplot length), dispersion was decreased after xamoterol, prenalterol, and prenalterol/ICI 118,551. Cardiac sequence analysis (differences between three adjacent beats; deltaRR vs. deltaRRn+1) assessed the short-term patterns of cardiac acceleration and deceleration; four patterns were identified: +/+ (a lengthening sequencing), +/- or -/+ (balanced sequences), and finally -/- (a shortening sequence). Cardiac acceleration or deceleration episodes (i.e., number of times deltaRR and deltaRRn+1 were altered in the same direction) were increased after salbutamol and prenalterol. In conclusion, partial agonism at either the cardiac beta1-adrenoceptor (xamoterol), beta2-adrenoceptor (salbutamol), and beta1- plus beta2-adrenoceptors (prenalterol) altered the autonomic balance toward sympathetic dominance in healthy volunteers; blockade of the beta2-adrenoceptor with the highly selective beta2-antagonist ICI 118,551 prevented the effects of salbutamol on HRV, attenuated the HRV effects of prenalterol, but had no effect on the actions of xamoterol. Agonism at both the beta1- and beta2-adrenoceptor reduced HRV in healthy subjects; the implications for the preventive use of the beta-adrenoceptor compounds in cardiovascular disease warrant further investigation.     

慢性心力衰竭患者心率变异性与心功能的相关性研究

目的 探讨慢性心力衰竭(CHF)患者心率变异性(heart rate variability,HRV)的特点及与心功能的相关性.方法 对59例CHF患者和65例健康对照者,行24小时动态心电图(Holter)监测,对比分析其HRV,并比较不同程度CHF患者HRV的差异.结果 HRV指标中,CHF组低频功率与高频功率比值...     

Subjective and neurovegetative changes in healthy volunteers and panic patients performing simulated public speaking

Drug-free symptomatic panic patients, drug-treated nonsymptomatic patients and healthy controls were submitted to simulated public speaking. Subjective anxiety, cognitive impairment and discomfort measured by the visual analog mood scale as well as skin conductance level were higher in symptomatic patients than in controls at the beginning of the experimental session, nonsymptomatic patients lying in between. Subjective sedation, spontaneous fluctuations of skin conductance, heart rate and blood pressure were similar in the three groups. Preparation and performance of speech decreased sedation while increasing anxiety, cognitive impairment, level and fluctuations of skin conductance, heart rate and blood pressure. Anxiety, cognitive impairment and conductance level were less increased in symptomatic patients than in controls. Electrodermal activity, but not cardiovascular measures of sympathetic arousal correlated with anticipatory anxiety. Chronic treatment with serotonin uptake inhibitors attenuated the differences between panic patients and controls, supporting the participation of serotonin in panic disorder.     

Effect of single-dose sertraline on the hypothalamus-pituitary-adrenal system, autonomic nervous system, and platelet function

OBJECTIVE: Pharmacological treatment with selective serotonin reuptake inhibitors (SSRIs) is thought to decrease coronary risk in patients with depressive disorder. Selective serotonin reuptake inhibitor intake may (1) attenuate the hypothalamus-pituitary-adrenal (HPA) system, (2) improve disturbances of the autonomous nervous system, and (3) dampen the aggregability of platelets. There is only limited information about the influence of acute treatment with SSRIs on these systems, which is especially important for the initiation of therapy in high-risk cardiac patients. We compared the reaction of these systems to physical stress with single-dose SSRI treatment (100 mg) with that of placebo treatment. METHODS: Using a double-blind, crossover, placebo-controlled design, we assessed HPA system activity via serum cortisol and corticotropin as well as sympathetic nervous system by determining serum norepinephrine and epinephrine levels at baseline and as a response to stress. Analysis of heart rate variability (HRV) provided information on sympathetic/parasympathetic balance. Platelet activity was measured via flow-cytometric determination of platelet surface activation markers along with the serotonin (5-HT) uptake of platelets. RESULTS: We studied 12 healthy young men under placebo and verum conditions. We found higher HPA system activity at baseline and after physical activity under sertraline when compared with placebo, no difference in sympathetic nervous system activity after physical exertion and only slightly heightened baseline epinephrine values after sertraline intake. No difference was seen between sertraline and placebo intake regarding platelet activity and 5-HT uptake, HRV, blood pressure, and HR. CONCLUSIONS: Initiating sertraline treatment increases HPA system activity and epinephrine concentrations. We found no clinically relevant effect of single-dose sertraline treatment on autonomous nervous function, platelet activity, or platelet 5-HT uptake. These findings may not be extrapolated to patients with affective or cardiac disorders or to other SSRIs.     

正常人心率减速力和心率变异性的变化及相关性

目的 测定不同年龄正常人心率减速力与心率变异性并分析其相关性,探讨其临床意义。方法 选取正常人90例,根据年龄将受试者分为青年组和老年组,进行24h动态心电图检查,离线计算DC、HRV时域指标及相关系数。结果 老年组DC和HRV值与青年组比较均降低,差异有统计学意义(P<0.05),且DC和HRV显著相关。结论 DC和HRV时域指标随着年龄的增加而减小,这些无创指标可以反映自主神经功能。     

Effects of Diazepam and Ethanol on Heart Rate and Galvanic Skin Responses

Abstract: Heart rate (HR), heart rate variability (HRV), and the amplitude and frequency of galvanic skin responses (GSR) were studied in nine healthy young males 2–3 hrs after oral administration of either placebo, diazepam (10 and 20 mg per 70 kg body weight), ethanol (0.78 and 1.22 ml/kg), or combined administration of diazepam (10 mg) and ethanol (0.78 ml/kg). When examinations were performed in resting subjects, ethanol produced significant increases in heart rate, as did combined administration of ethanol and diazepam. Heart rate variability, supposedly correlated to reaction time, was reduced by combined administration of the two drugs. The frequency of the GSR was reduced by both ethanol and 20 mg diazepam, while the amplitude was increased by 10 mg diazepam and reduced by 20 mg diazepam, although not significantly, and was reduced on one occasion by ethanol. Stimulation by mental arithmetic increased all parameters, and more so after drug treatment than after placebo. The results are discussed in relation to the possible effects of diazepam on the autonomic nervous system, and also in relation to the psychophysiological activation theory which presupposes that increased activation is related to increased sympathetic activity. It is concluded that the parameters used are not reliable as indicators of whether a drug is deactivating or not.     

高血压病并发冠心病患者的心率变异性与心律失常分析

目的 探讨高血压病并发冠心病患者的自主神经活动和心律失常的特点.方法 对52例原发性高血压(EH)患者、44例冠心病(CHD)患者和56例EH并发CHD患者与34例健康老年人的心率变异性(HRV)进行对比研究.结果 EH组和CHD组与对照组HRV时域法所有参数差异均有显著性(P＜0.05);EH并发CHD组与对照组比较,各参数差异均有非常显著意义(P＜0.01);但不同疾病组间比较,差异均无显著性(P＞0.05).3个疾病组与对照组比较,房性早搏、房性心动过速和室性早搏的发生率均有极显著性差异(P＜0.01);而EH组、CHD组及EH CHD组间,除外CHD组与EH CHD组房性早搏的发生率有显著性差异外(P＜0.05),其余差异均无显著性.结论 高血压病患者和冠心病患者的自主神经功能受损,心律失常发生率增加(以房性早搏最常见,其次为室性早搏);当高血压病患者并发冠心病时这种受损更加明显,其迷走神经张力降低,交感神经紧张性相对增高是导致老年患者心率变异性降低的主要原因和心律失常的可能因素.     

The relationship between traffic-related air pollutants and cardiac autonomic function in a panel of healthy adults: a further analysis with existing data

Context: Epidemiological studies have linked particulate matter (PM) and carbon monoxide (CO) exposures with alterations in cardiac autonomic function as measured by heart rate variability (HRV) in populations. Recently, we reported association of several HRV indices with marked changes in particulate air pollution around the Beijing 2008 Olympic Games in a panel of healthy adults.

Objective: We further investigated the cardiac effects of traffic-related air pollutants over wide exposure ranges with expanded data set in this panel of healthy adults.

Methods: We obtained real-time data on nine taxi drivers’ in-car exposures to PM ≤2.5?µm in aerodynamic diameter (PM_2.5) and CO and on multiple HRV indices during a separate daily work shift in four study periods with dramatically changing air pollution levels around the Beijing 2008 Olympic Games. Mixed effect models and a loess smoother method were used to investigate the associations of exposures with HRV indices.

Results: Results showed overall negative associations of traffic-related air pollutants with HRV indices across periods, as well as differences in period-specific and individual associations. After stratifying the individuals into two different response groups (positive/negative), cardiac effects of air pollutants became stronger within each group. Exposure–response modeling identified changed curvilinear relationships between air pollution exposures and HRV indices with threshold effects.

Discussion and conclusion: Our results support the association of exposure to traffic-related air pollution with altered cardiac autonomic function in young healthy adults free of cardiovascular compromises. These results suggest a complicated mechanism that traffic-related air pollutants influence the cardiovascular system of healthy adults.     

Acute effects of a single oral dose of carvedilol on cardiac sympathovagal balance in man

Modulation of autonomic activity is considered to be a prognostic marker in patients with cardiovascular disease. The aim of the present study was to evaluate the modulation of sympathovagal balance after single-dose administration of carvedilol using various autonomic tests as challenges of sympathovagal balance. We conducted a randomized double-blind, placebo-controlled study in 18 male volunteers and applied a crossover design. While heart rate variability (HRV) remained unchanged in 24-hour measurements, modulatory effects on sympathovagal balance were demonstrated in controlled autonomic maneuvers at expected maximal drug levels of carvedilol: time-dependent HRV parameters indicative of vagal tone were increased during controlled breathing (15 cycles/min) in the supine body position by carvedilol. The percentage of successive normal RR intervals > 50 ms (pNN50) was increased to 39.8+/-5.1 vs. 32.7+/-4.7% in the placebo group (p < 0.05), root mean square successive differences (rMSSD) to 81.5+/-10.8 vs. 69.3+/-9.1 ms (p < 0.05 vs. placebo). In contrast, carvedilol versus placebo significantly reduced time- and frequency-domain parameters after an active standing-up procedure. This included rMSSD (26.5+/-2.8 ms vs. 34.9+/-3.8 ms), pNN50 (6.9+/-2.2% vs. 12.4+/-2.5%). total power (4329+/-592 ms2 vs. 6428+/-1158 ms2), low frequency (1472+/-179 ms2 vs. 2093+/-284 ms2) and high frequency power (251+/-42 ms2 vs. 353+/-92 ms2) of heart rate variability. Apparently, the effects of even small doses of carvedilol, too low to induce effects detectable in the 24-hour analysis of HRV testing, can be detected on controlled maneuvers of autonomic because of their ability to modulate autonomic balance. Under conditions of vagal stimulation, a potentially beneficial augmentation of HRV parameters indicative for this component is induced by carvedilol, while under conditions of sympathetic activation, carvedilol effects seem opposite. Interpretation of the latter results, in particular, requires further investigation.     

Effects of physostigmine on scopolamine–induced changes in quantitative electroencephalogram and cognitive performance

The effects of physostigmine on scopolamine-induced changes were investigated in a randomized, double-blind cross-over study utilizing quantitative electroencephalogram (qEEG) and cognitive tasks. Ten healthy male volunteers received scopolamine 0·6 mg subcutaneously. After 90 min, single doses of either 0·5, 1·0 and 2·0 mg physostigmine salicylate or placebo were administered subcutaneously in randomized order. qEEG, cognitive function and the visual analogue scale were recorded before and at 1, 2, 3, 4, 6, and 8 h after scopolamine administration; that was 0·5, 1·5, 2·5, 4·5, and 6·5 h after physostigmine administration. Scopolamine produced an increase in delta (1·25–4·50 Hz) and theta power (4·75–6·75 Hz) in qEEG 1 h after administration compared to baseline, while physostigmine decreased the spectral delta power density in qEEG compared to placebo. The maximal effect of physostigmine was seen up to 1·5 h after injection. A dose-dependent reversal of the scopolamine induced decrements in cognitive performance was found 0·5 h after administration of physostigmine. Psychometric tests sensitively discriminated between the doses of physostigmine, and showed dose- and time-dependent effects. The results suggest that physostigmine may reverse the scopolamine-induced changes in both qEEG and cognitive function. This reversal was temporary and of short duration. © 1998 John Wiley & Sons, Ltd.