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Biomedical subjects

D Warot

Publications and source records attributed to D Warot.

At least 19 recordsLinked to original sources
PubMed1997

Sensitivity and specificity to amphetamine of a French version of the 49-item form of the addiction research center inventory.

The main metrological characteristics of a French version of the 49-item addiction research center inventory (ARCI) were evaluated using data collected in three controlled studies in healthy subjects. An analysis of variance showed no study effect, so the three studies were pooled. The test-retest reliability coefficients after placebo evaluated by a Spearman rank correlation test were 0.64 (P < 0.0001) for subscale A, 0.49 (P < 0.0001) for subscale BG, 0.55 (P < 0.0001) for MBG, 0.58 (P < 0.0001) for PCAG and 0.27 for LSD (not significant). Using the same test, the test-retest reliability coefficients after amphetamine were 0.73 (P < 0.0001) for subscale A, 0.61 (P < 0.0001) for subscale BG, 0.71 (P < 0.0001) for MBG, 0.46 (P < 0.0001) for PCAG and 0.66 for LSD (P < 0.0001). In order to assess the predictive validity of the translated questionnaire, areas under curves were calculated from the ROC diagrams for the three scores, amphetamine (A), benzedrine group (BG) and morphine benzedrine group (MBG). Two criteria validity were used: the desire to take amphetamine another time and the discrimination of the allocated treatment (amphetamine or placebo). The calculated areas under curves indicated a good capacity of prediction of the three ARCI subscales (A, BG, MBG) for both criteria.

Adolescent↗
PubMed1996

Effects of befloxatone, a reversible selective monoamine oxidase-A inhibitor, on psychomotor function and memory in healthy subjects.

Befloxatone is a new reversible and selective monoamine oxidase (MAO-A) inhibitor that has been shown to have antidepressant activity in various animal models. To assess the effects of single oral doses of befloxatone (5, 10, and 20 mg) on psychomotor performance and memory, a randomized, double-blind, five-way, crossover study with both placebo and amitriptyline (50 mg) was carried out in 15 healthy male volunteers. Psychomotor and cognitive functions were evaluated using both objective measures, including Critical Flicker Frequency (CFF), Choice Reaction Time (CRT), Digit Symbol Substitution Test (DSST), and a picture memory test and subjective measures, including Visual Analog Scales (VAS) and Addiction Research Center Inventory (ARCI), before and 2, 4, and 8 hours after administration. Pupil diameter was recorded by videopupillography. Single doses of befloxatone from 5 to 20 mg did not result in any detrimental effects on skilled performance and memory. In contrast, amitriptyline significantly impaired arousal (CFF), speed of reaction (CRT), information processing (DSST) and long-term memory (delayed free recall of pictures) and produced subjective sedation from 2 to 8 hours after administration. At the doses studied amitriptyline induced miosis but befloxatone did not modify pupil diameter. There was no evidence in this study to suggest that befloxatone, at the doses studied, has any sedative or amnesic effects in healthy subjects.

Adult↗
PubMed1994

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

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

Adult↗
PubMed1994

The pharmacokinetics and electrocardiographic effects of chloroquine in healthy subjects.

Chloroquine prophylaxis was administered to 3 healthy male volunteers at 100 mg base/day for 25 days, followed by the curative dose at 25 mg base/kg for 3 days. Subjects attained effective chloroquine (mean = 50 micrograms/l) and desethylchloroquine (mean = 17 micrograms/l) concentrations by the 3rd week of prophylaxis, underlining the need to start chloroquine prophylaxis two weeks before travel. On the second day of the treatment period, hourly electrocardiographic monitoring showed a diminution of the T wave and prolongation of the QTc interval, manifesting cumulatively during the 3 days' curative dose, but with no cardiac symptoms. A dose-dependent cumulative effect of chloroquine was demonstrated with higher blood concentrations during the treatment period. Electrocardiographic readings spontaneously normalized after the treatment period as drug concentrations diminished progressively.

Adult↗
PubMed1993

Comparison of the effects of zolpidem and triazolam on memory functions, psychomotor performances, and postural sway in healthy subjects.

Zolpidem is a rapid-onset, short-duration imidazopyridine hypnotic drug and is specific agonist of the omega-1 (BZD1) receptors. Its hypnotic characteristics resemble those of triazolam. The aims of this study were to assess the effects of zolpidem on memory (the main objective), psychomotor performances, and postural sway (secondary objectives) in 18 healthy subjects and to compare them with those of triazolam and placebo. Short- and long-term memory (paired words associate and pictures test), psychomotor performances (critical flicker fusion frequency, choice reaction time, digit symbol substitution test), and postural sway were evaluated before and 1.5, 4, 6, and 8 h after the administration of a single dose of zolpidem (10 mg), triazolam (0.25 mg), and placebo. For each assessment, the maximal effect for both hypnotic drugs occurred 1.5 hour after intake. Both drugs decreased psychomotor performance, impaired memory, and increased postural sway. The effects of both hypnotic agents were short lasting, and no alterations were found 6 and 8 hours, respectively, after drug intake. No clinically relevant differences were found between zolpidem and triazolam for memory, psychomotor performance, postural sway, or adverse effects. It may be concluded that zolpidem, like triazolam, impairs short- and long-term memory, psychomotor performances, and postural sway and that these effects are of short duration.

Adult↗
PubMed1992

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.

Acoustic Stimulation↗
PubMed1991

[Pharmacology of the memory. Review of cognition activator pharmacology].

The pharmacology of memory is fraught with problems. For one thing, the lack of consensus on the definition of memory and the absence of reference compound create clinical validation problems for new drugs. Then, it is difficult to predict clinical effectiveness on the basis of animal experiments and data obtained from healthy subjects, and this is due to the lack of analogy between animal models and clinical situations. Finally, to this must be added the complexity and variety of the possible modes of action of the agents under study. Thus, the pharmacology of cognition activators is closely dependent upon both fundamental research and clinical research.

Animals↗
PubMed1990

Lack of interaction between disulfiram and alprazolam in alcoholic patients.

Certain interactions between disulfiram and benzodiazepines, especially diazepam and chlordiazepoxide, have previously been reported. The influence of disulfiram on the pharmacokinetics of alprazolam, a triazolobenzodiazepine, metabolized by hepatic microsomal oxidation, has been evaluated in 11 chronic alcoholic patients (6 males, 5 females) undergoing treatment for the alcohol withdrawal syndrome. Each patient received alprazolam 2 mg on the first day (control) followed by two weeks of treatment with disulfiram 0.5 g/d, and then further oral dose of alprazolam 2 mg. No significant change was found in any of the kinetic parameters. Thus, a therapeutic dose of disulfiram did not significantly alter the clearance or half-life of alprazolam in chronic alcoholic patients.

Adult↗
PubMed1990

Daytime wakefulness following a bedtime oral dose of zolpidem 20 mg, flunitrazepam 2 mg and placebo.

1. The effects of zolpidem 20 mg, flunitrazepam 2 mg and placebo, administered at bed time, were studied in 12 healthy young male volunteers. 2. The assessments included, at awakening, subjective ratings of overnight sleep, cognitive function, psychomotor performance (digit symbol substitution, choice reaction time, flicker fusion threshold), subjective ratings of alertness, and plasma assay of residual drug concentration. Daytime sleep propensity during the day after dosing was evaluated with the multiple sleep latency test. 3. Compared with placebo, both active drugs improved subjective assessment of the ease of getting to sleep. At awakening, under flunitrazepam treatment, the reduction of performance, on memory and psychomotor tests, paralleled an increased subjective rating of sleepiness, but zolpidem treatment left subjects unimpaired compared with placebo. Similarly, daytime sleep propensity was enhanced throughout the following day under flunitrazepam treatment, but not under zolpidem treatment. Plasma assay for residual drug concentration at awakening found significant amounts of flunitrazepam and marginal amounts of zolpidem. 4. Results indicate that zolpidem 20 mg is devoid of residual effects in a range of tasks that were sensitive enough to demonstrate a prolonged wakefulness impairment following flunitrzepam 2 mg in healthy volunteers.

Administration, Oral↗
PubMed1989

Assessment of erectogenic drugs by numeric plethysmography.

A method of assessment of the erection in man, using numeric penile plethysmography, is presented. The data concerning the sensor, the electronic circuit, and the computer interfacing with an IBM PC are described. As a validation of this method, apomorphine (0.009 mg/kg) was tested in a double-blind, placebo-controlled study, carried out in healthy volunteers. Apomorphine induced an erection starting, as a mean, at the fourth minute postinjection. The treatment increased the penis volume without any other stimulation (p = 0.0008) and potentiated the physiologic response induced by visual erotic stimulation (p = 0.0012). The limits of plethysmography are discussed in reference to rigidimetry.

Adult↗
PubMed1989

Effects of dihydroergotamine on psychomotor function, neuroendocrine parameters and blood pressure, in healthy volunteers.

Following the infusion of 15 micrograms/kg of dihydroergotamine (DHE) a 50-fold rise in growth hormone plasma levels was observed in 9 healthy volunteers. Prolactin (PRL) secretion was depressed 240 minutes post infusion. For 170 min, diastolic blood pressure was increased reaching a peak of +19 mmHg at the end of the infusion. Mild sedation and nausea were induced by the treatment for a total duration of 60 min.

Adult↗
PubMed1988

Assessment of erectogenic properties of apomorphine and yohimbine in man.

1. In a four period, double-blind, placebo-controlled study, apomorphine (0.009 mg kg-1 subcutaneous route) and yohimbine (0.30 mg kg-1 i.v. route) were administered to 10 male healthy volunteers. Penile circumference was monitored using plethysmography and subjective sexual arousal was self-assessed. Data were collected before, during and after a stimulation session during which 50 erotic slides were projected to the subjects. 2. Apomorphine induced an erection starting from the fourth minute post-injection, and potentiated the visually-induced response. Self assessment showed increased tumescence and rigidity without modifications of sexual arousal. 3. Yohimbine did not modify penile diameter without stimulation and did not affect the physiological response to erotic stimuli. 'Sexual excitement' was decreased by yohimbine during the post-stimulation phase. One subject experienced severe anxiety while he was infused with yohimbine. 4. These results are discussed with reference to animal data and to recent studies carried out in impotent patients.

Adult↗
PubMed1987

Troleandomycin-triazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation.

Seven healthy volunteers received a single oral dose of triazolam 0.25 mg after 7 days on troleandomycin 2 g/day p.o. or placebo in a double-blind cross-over study. Plasma triazolam and psychometric and memory tests (including Critical Flicker Fusion threshold, Choice Reaction Time, Digit Symbol Substitution and Self-Rating Scales) were assessed at regular intervals after the final treatment. Troleandomycin was found to prolong the psychomotor impairment and amnesia produced by triazolam. There was a significant enhancement of the AUC, the peak concentration and the delay to tmax of triazolam after 7 days treatment with troleandomycin compared to placebo. Thus, there is a pharmacokinetic interaction, and the combination of triazolam and troleandomycin should be avoided or the dose of triazolam should be adjusted. The most likely mechanism is a diminished hepatic first-pass effect, and a decrease in the apparent oral clearance of triazolam.

Adult↗
PubMed1987

Lack of sleep-inducing properties of propranolol (80 mg) in chronic insomniacs previously treated by common hypnotic medications.

In a double-blind, placebo-controlled crossover trial, propranolol 80 mg did not show any hypnotic properties and even increased the insomnia in a sample of 37 patients previously treated chronically with hypnotic medication (mostly benzodiazepines). This worsening of the insomnia is consistent with the observations of sleep disturbance at the beginning of treatment with beta-blocking drugs. This lack of efficacy suggests that the anti-stress or anxiolytic properties of propranolol do not apply to the rebound insomnia seen when stopping treatment with hypnotic drugs.

Adult↗
PubMed1987

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

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

Adult↗