Biomedical subjects

A Patat

Publications and source records attributed to A Patat.

At least 19 recordsLinked to original sources

PubMed2002

A review of the pharmacokinetics, tolerability and pharmacodynamics of amisulpride in healthy volunteers.

Amisulpride binds selectively to dopamine D(2) and D(3) receptors in the limbic system. Low doses of amisulpride preferentially block presynaptic D(2)/D(3)-dopamine autoreceptors, thereby enhancing dopaminergic transmission, whereas higher doses block postsynaptic receptors, thus inhibiting dopaminergic hyperactivity. Amisulpride is clinically effective on the negative symptoms of acute schizophrenia exacerbations at low dosages (50-300 mg/day), and also on the positive symptoms of the disease at high dosages (400-800 mg/day). Nineteen clinical studies involving 358 volunteers have investigated the pharmacokinetics, pharmacodynamics and tolerability of amisulpride. Amisulpride shows linear pharmacokinetics, a bioavailability of 48%, low protein binding (17%) and an elimination half-life of approximately 12 h. It is predominantly eliminated in the urine as the parent compound. It exhibits no significant detrimental effects in psychometric or memory tests up to the dose of 400 mg/day, inducing only mild impairment at high doses, whereas EEG data suggest an alertness-enhancing effect at low doses (<or= 50 mg). Moreover, amisulpride does not potentiate the depressant effects on the central nervous system of alcohol and lorazepam. This tolerability profile is clearly better than that of haloperidol 4 mg/day and is consistent with a weak blocking effect on striatal D(2) receptors. In summary, studies in humans have shown that amisulpride is free of behavioural toxicity at doses exerting clear antipsychotic efficacy and confirm that its CNS effects may vary with the dose administered.

Amisulpride↗

PubMed1999

Lack of behavioural toxicity of mizolastine: a review of the clinical pharmacology studies.

First-generation H1 antihistamines were associated with major sedative side-effects which were heavily disruptive to young active and aged patients when performing everyday activities. Mizolastine is a potent and selective H1-receptor antagonist which slowly penetrates into the brain and thus lacks the sedative effects of earlier antihistamines. In this paper we present an overview of five clinical pharmacology studies which were carried out with a view to assessing mizolastine effects on psychomotor and skilled performances, and on cognitive functions in young and aged subjects. The studies were all randomized, double-blind, placebo and (with the exception of one) active-drug controlled, cross-over studies. A total of 76 young and 15 aged subjects were enrolled. Two studies evaluated mizolastine over a range of doses (5-45 mg), and three involved a single or multiple administrations of the therapeutic dose (10 mg/day). Comparators were first generation (clemastine, tripolidine) and second generation (terfenadine, cetirizine) antihistamines. Drug effects were evaluated through standardized psychometric and memory tests, and subjective self-ratings (visual analogue scales). In two studies, driving performance was assessed using an actual driving test. Two studies investigated drug interaction with depressants of the central nervous system such as alcohol and lorazepam. The results of the five reported studies were consistent in that mizolastine showed to be free from sedative effects when administered at the therapeutic dose. As with other newly developed antihistamines, some changes occurred at higher dose levels. At the therapeutic dose mizolastine did not alter driving performance and did not potentiate the depressant effects of alcohol and lorazepam. Mizolastine was shown to be free from sedative effects that could affect the safe performance of everyday life activities in young and aged patients when administered at the therapeutic dose.

Adolescent↗

PubMed1999

Psychomotor, Cognitive, extrapyramidal, and affective functions of healthy volunteers during treatment with an atypical (amisulpride) and a classic (haloperidol) antipsychotic.

The primary objective of this study was to compare the objective and subjective effects of amisulpride with those of a classic antipsychotic, haloperidol, when both were given to healthy volunteers in representative therapeutic doses over 5 days. The secondary objective was to compare the effects of relatively low and high doses of amisulpride to confirm the suspected duality of its pharmacologic activity. Twenty-one subjects participated in the four-way, randomized, double-blind, crossover study with repeated daily doses of amisulpride 50 mg, amisulpride 400 mg, haloperidol 4 mg, and placebo. Subjects were institutionalized during treatment periods and were under 24-hour medical supervision. They underwent a series of psychomotor and cognitive tests 1 hour before and 3 and 6 hours after dosing on days 1 and 5. Their extrapyramidal disturbances and drug-related feelings were assessed at the end of each replication. Psychiatric interviews and ratings of depression, subjective well-being, and negative symptoms occurred on day 4. Amisulpride 50 mg had no significant effect on any parameter. Amisulpride 400 mg had several adverse effects on psychomotor and, although less severe, on cognitive performance on the fifth day only. Amisulpride 400 mg produced no significant extrapyramidal disturbances in the group as a whole, although it may have in some individual subjects. Also, it produced no signs of mental disturbances on clinical rating scales or during a structured psychiatric interview. Haloperidol ubiquitously impaired psychomotor and cognitive performance in a similar fashion after the first and the final doses. It produced extrapyramidal disturbances in nearly every subject, the most common being akathisia and the most severe, in the case of one individual, being acute dystonia. Unlike amisulpride, haloperidol produced a number of mental disturbances, the most noteworthy being negative symptoms. Amisulpride seems to be a well-tolerated drug. Its side effects should be much less troublesome to patients using the drug on a long-term basis than those of classic antipsychotics, like haloperidol.

Adult↗

PubMed1999

Effects of tiapride on electroencephalograms and cognitive functions in the elderly.

Tiapride is a substituted benzamide with selective dopamine D2 and D3-antagonist properties which appears to have preferential affinity for extra-striatal dopamine receptors. Tiapride is used in the treatment of agitation, aggressiveness and anxiety in the elderly. To define the effects of a single dose of tiapride 100 mg on psychomotor performance and cognitive functions and electroencephalogram (EEG), a randomized, double-blind, three-way crossover, placebo-controlled study using lorazepam 1 mg as a positive control was carried out in 12 elderly individuals (six women and six men, mean age +/- SD: 69 +/- 3 years). A 1-week wash-out interval was allowed between each administration. Psychomotor and cognitive functions were assessed using both objective [EEG, critical flicker fusion, simple reaction time, tapping, body sway, continuous performance task (CPT), digit symbol substitution test, Sternberg memory scanning and a learning memory test using word lists] and subjective (visual analogue scales) measures before and up to 6 h after dosing. Tiapride was devoid of any detrimental or sedative effects on EEG and all of the performance tasks used and did not impair memory compared with-placebo. In contrast, a single dose of lorazepam produced significant deleterious effects on psychomotor performance (decrease in tapping and in sustained attention (CPT) and an increase in reaction time and body sway), and sedative effects on EEG (significant increase in delta and decrease in alpha waves) as well as significant impairment in working memory (Sternberg) and anterograde amnesia (decrease in immediate and delayed free recall) up to 6 h after dosing compared with placebo and tiapride. In conclusion, the present study showed that in contrast to lorazepam 1 mg there is no evidence to suggest that a single dose of tiapride 100 mg has any sedative and amnestic effects in the elderly which may interfere with everyday life activities.

Aged↗

PubMed1999

Effects of 50mg amisulpride on EEG, psychomotor and cognitive functions in healthy sleep-deprived subjects.

Amisulpride, a substituted benzamide, binds selectively to the dopamine D2- and D3-receptors. It has higher affinity for limbic compared to striatal dopamine receptors in vivo. At low doses, amisulpride facilitates dopamine transmission via a selective blockade of presynaptic D2- and D3-receptors. Amisulpride is an active antipsychotic compound effective at low doses for negative symptoms and at high doses for positive symptoms of schizophrenia. The CNS profile of multiple doses of a low dosage regimen of amisulpride (50 mg once daily for 4 days) was assessed in a randomised, double-blind, 3-way crossover, placebo-controlled study carried out in 12 young sleep-deprived (for 36 h) subjects, using EEG and various measures of psychomotor and cognitive functions. Caffeine slow release (600 mg) was used as a positive reference. Multiple doses of 50 mg amisulpride once daily were devoid of any detrimental effects on EEG and psychomotor performance and cognitive function after total sleep deprivation. In addition, 50mg amisulpride partially antagonized the deleterious effects of sleep deprivation on EEG and subjective sedation as shown by trends, and a significant increase in EEG relative beta power and a decrease in subjective sedation. These effects were more pronounced at the end of sleep deprivation, suggesting possible alerting effects of amisulpride at this dose level. Caffeine significantly antagonized the detrimental effects of sleep deprivation on vigilance (increase in EEG beta waves, speed of reaction, sustained attention and reduction in subjective sedation). In conclusion, the present results demonstrate that 50 mg amisulpride is devoid of detrimental effects on EEG, psychomotor and cognitive performance after sleep deprivation, a situation well-known to amplify such effects if they exist. Moreover, some data suggest possible alerting effects of this low dosage regimen of amisulpride.

Adult↗

PubMed1998

Absolute bioavailability and electroencephalographic effects of conventional and extended-release formulations of venlafaxine in healthy subjects.

Venlafaxine is currently marketed for treatment of depressive disorders as a conventional tablet formulation with a twice or three times daily dosage regimen. The absolute bioavailability of the conventional (CF) and extended-release (XR) formulations and their effects on electroencephalograms (EEG) and on a visual analog scale (VAS) for nausea were assessed in a randomized, double-blind, four-way crossover, placebo-controlled study of 16 healthy young men who were given either a single oral dose of 50 mg of CF venlafaxine, 75 mg of XR venlafaxine, or an intravenous dose of 10 mg of venlafaxine, or a placebo at 1-week intervals. The absolute bioavailability of venlafaxine was between 40% and 45% and was similar for both the CF and XR formulations. Venlafaxine produced central effects of a desipramine-like antidepressant. Regardless of formulation tested, the main EEG changes were an increase in fast beta (20-30 Hz) energy, which was more pronounced over the frontotemporal regions and extended within the full beta range (16-40 Hz). Maximum effect was reached at 6 hours for the CF and reached a plateau from 10 to 24 hours for the XR formulation. A dose-proportional increase in central activity, expressed as area under the effect curve (AUE) of the beta band, was observed between the CF (50 mg) and XR (75 mg) formulations. Compared with the CF tablet, the XR formulation also produced a much less intense maximum effect and a decrease of 63% in the AUE of nausea normalized by dose. The XR formulation has the same absolute bioavailability and the same central activity as assessed by EEG, but produced less intensive nausea than CF venlafaxine. The present findings suggest that a once-daily dosage regimen should be sufficient. This was confirmed by several clinical trials in depressive patients.

Adult↗

PubMed1998

Cognitive performance in elderly subjects after a single dose of befloxatone, a new reversible selective monoamine oxidase A inhibitor.

BACKGROUND: Patients with depression often have cognitive and psychomotor performance impairments. Antidepressive treatments can correct these deficits, provided sedative and anticholinergic adverse effects do not add to the preexisting condition, particularly in elderly patients. Newly developed antidepressants therefore should be without deleterious effects on cognitive functions, including memory. Befloxatone is a new antidepressant with a potent, selective, competitive, and reversible inhibitory activity on the A isoform of monoamine oxidase (MAO-A). METHODS: The effects on cognition and psychomotor performance of single oral doses of befloxatone (10 mg) and amitriptyline (50 mg) were compared in a randomized, double-blind, placebo-controlled, three-way crossover design trial in 12 healthy elderly (65 to 85 years) volunteers. The performances of the subjects were evaluated by a comprehensive battery of validated psychometric tests that explored alertness, psychomotor performance, information processing, and memory. Subjective feelings on mood and sleep were rated on visual analog scales. MAO-A inhibition was estimated by multiple titrations of 3,4-dihydrophenylglycol (DHPG) in plasma. RESULTS: Amitriptyline displayed the expected deleterious effects on performance tasks, critical flicker fusion threshold, digit symbol substitution, and body sway, and it deteriorated memory (immediate and delayed free recall of words). In contrast, befloxatone did not impair cognition or psychomotor performance but instead significantly improved the delayed free recall. Amitriptyline adversely affected subjective feelings of alertness and contentedness, but befloxatone permitted sustained alertness and did not alter other subjective feelings or sleep. Concurrently, a single dose of 10 mg befloxatone markedly decreased the DHPG concentration in plasma. CONCLUSION: Contrary to tricyclic antidepressants, whose deleterious effects are greater in elderly subjects, this study demonstrated the safety of befloxatone on cognition and psychomotor performance in elderly subjects.

Aged↗

PubMed1998

Clinical pharmacology of befloxatone: a brief review.

Clinical pharmacology studies of befloxatone, a new selective reversible inhibitor of monoamine oxidase-A (MAO-A), have addressed safety, with special emphasis on tyramine interactions, and have also investigated pharmacokinetics (PK) and pharmacodynamics in terms of both MAO-A inhibition (using 3,4-dihydroxyphenylglycol, DHPG, as a pharmacological activity marker) and effects on psychomotor and cognitive function, in young and elderly healthy volunteers. Clinical and laboratory safety data were satisfactory in healthy volunteers given single doses of up to 160 mg or repeated doses of up to 80 mg/day for 7 days. Tyramine interaction studies showed that the expected potentiation of the tyramine pressor effect occurred with a safety margin that was so wide as to make dietary restrictions unnecessary with dosages of up to 20 mg once daily in clinical settings. Absorption was rapid (tmax = 2 h), terminal halflife was about 11 h, and PK parameters increased linearly with the dose. Befloxatone induced a dose-dependent decrease in plasma DHPG levels from 2.5 mg upwards, and a 10-mg dose provided sub-maximal activity (80% DHPG decrease) of 24 h duration. No sedative or stimulant effects were detected using several batteries of psychometric tests. Befloxatone was devoid of deleterious effects on memory in young volunteers, and exhibited the EEG profile of a non-sedative antidepressant. In summary, available clinical pharmacology studies confirm that befloxatone is a safe and potent RIMA with no potential for inducing deleterious CNS effects.

Adult↗

PubMed1998

Effect of bromazepam versus placebo on inhibition and waiting capacity in young women with traits of anxiety.

The effect of 3 dosages of bromazepam administered as single oral doses (1.5, 3 and 6 mg) on anxious inhibition phenomena was studied in a population of 16 young women (18-30 years) with anxiety-traits, selected on the criteria of Cattell's anxiety scale supported by two personality inventory (Eysenck's, MMPI). A double-blind, placebo study design was chosen. The main assessment criteria were based on the go/no-go test (Logan's procedure), slow response rate (SRR) and a task of forced or unforced decision (use of the CFF). Attentional processes and declarative memory were analyzed as secondary criteria. None of the three dosages modified inhibition or acting-out. Sustained attention was reduced with 1.5 mg and 6 mg, as was memory performance with 3 and 6 mg, 3.5 h after drug administration. In contradistinction with studies carried out in healthy volunteers or with other benzodiazepine compounds, bromazepam at single low dosages does not modify inhibition capacity in these subjects with traits of anxiety, in this particular procedure.

Administration, Oral↗

PubMed1997

Effects of haloperidol and amisulpride on motor and cognitive skill learning in healthy volunteers.

The effects of a typical neuroleptic, haloperidol (1 and 2 mg orally), of an atypical neuroleptic, amisulpride (50 and 100 mg) and of a placebo on motor and cognitive skill learning were assessed in 60 healthy volunteers using repeated testing on the Tower of Toronto puzzle. Subjects were asked to solve three blocks of eight trials and, at distance from drug administration, a fourth block. The puzzle was connected to a computer in order to obtain a precise timing of individual moves. Two components of cognitive skill learning were assessed, the ability to learn to solve the puzzle and the acquisition of a problem-solving routine. Subjective feelings of effort and automatisation of the task were assessed using a questionnaire. Like placebo-treated subjects, neuroleptic-treated subjects were able to acquire a motor skill, to learn to solve the puzzle and to acquire a routine. However, haloperidol 2 mg-treated subjects needed significantly more moves to solve the puzzle in blocks 3 and 4, some of them having routinised a non-optimal solution. A significant cognitive slowing was observed in the haloperidol 1 mg group in block 4. The performance pattern and verbal reports suggested that haloperidol impaired the higher cognitive functions such as the ability to shift from one strategy to another and/or to assess one's performance accurately, possibly leading to the development of compensatory strategies. The only deleterious amisulpride effect was a cognitive slowing in block 4, which was observed in the lower dose group.

Adult↗

PubMed1997

[Baseline blood pressure in healthy normotensive volunteers].

UNLABELLED: The aim of this study was to define the reproducibility and the time required to obtain a stable baseline level of blood pressure (BP) in normotensive volunteers during a phase I trial. Blood pressure was recorded automatically (Dinamap and Marquette monitors) every 5 min during a 2-hour period and manually (Random zero device) at T20, T60 and T120, twice at a one-week interval, under similar study conditions (6 in the morning, 7 in the afternoon) in supine position in 13 normotensive men (aged 20 to 28). The average BP was compared using a 3-way ANOVA (subject, time, week). 1.SBP/DBP decreased significantly (p < 0.001) from one week to the other and SBP, but not DBP, decreased significantly over time up to T75 (p < 0.001): [table: see text] 2. SBP was significantly higher in the morning than in the afternoon during both weeks (p = 0.001). The decrease in SBP with rest was only observed in the morning (p = 0.00001). 3. Reproducibility and change over time and period did not significantly differ between manual and oscillometric methods. The best reproducibility of T75 was obtained with the mean of 3 automatic values (T70, T75, T80). CONCLUSION: in normotensive subjects, BP decreased from one period to the next and with rest. The baseline value of BP was obtained from T75 with the best reproducibility when baseline BP level is defined by 3 automatic values.

Adult↗

PubMed1996

Central benzodiazepine receptor occupancy by zolpidem in the human brain as assessed by positron emission tomography.

The central benzodiazepine receptor occupancy by zolpidem in man is unknown. The present study used positron emission tomography (PET) and [11C]flumazenil to assess in five healthy volunteers, central benzodiazepine receptor occupancy in brain regions with high receptor densities 1 h following an acute oral administration of twice the usual hypnotic dose of zolpidem (20 mg). Receptor occupancy was measured in five discrete structures (middle frontal gyrus, middle temporal gyrus, posterior occipital cortex, lateral parietal cortex, and cerebellar cortex) and in a large neocortical area as the fractional change in the [11C]flumazenil bound/free ratio for the interval 15-40 min post-administration of the radiotracer. The free-radioligand concentration was estimated from the pons, a reference structure virtually devoid of central benzodiazepine receptor. With individual pons values, mean occupancy was about 21% but with spurious inter-subject variability. With pons values averaged across the five subjects and separately for control and treated condition, the occupancy was (mean +/- S.D.) 27 +/- 11% for the whole neocortex, and ranged from 26 to 29% in the five discrete structures (P < 0.01). By showing hypnotic effect at moderate occupancies, this study directly provides evidence for the full-agonist properties of zolpidem in human.

Adult↗

PubMed1996

Pharmacodynamics and pharmacokinetics of two dose regimens of befloxatone, a new reversible and selective monoamine oxidase inhibitor, at steady state in healthy volunteers.

The pharmacodynamic equipotency of 2 dose regimens (5 mg twice daily versus 10 mg once daily) of befloxatone, a new reversible and selective monoamine oxidase A (MAO-A) inhibitor, after single and multiple doses for 6 days was examined in a randomized, double-blind, three-way crossover, placebo-controlled trial of 12 healthy volunteers. Plasma levels of the deaminated metabolite 3-4 dihydroxyphenylglycol (DHPG), as measured by high-performance liquid chromatography (HPLC) with coulometric electrochemical detection, were used as an index of MAO inhibition. A single dose of befloxatone produced a significant dose-related reduction in plasma DHPG levels, as shown by the decrease in the 24-hour area under the concentration-time curve (AUC0-24) of DHPG, which peaked 2 hours after administration and persisted over 24 hours. Both dose regimens provided equipotent extent and duration of MAO-A inhibition at steady state, suggesting a once daily dosage should be sufficient for most patients. The pharmacokinetic bioavailability at steady state of both dose regimens was also similar. The concentration-time effect curve after a single dose revealed a hysteresis corresponding to the delay necessary to elicit MAO inhibition and/or elimination of DHPG. The relationship between plasma levels of DHPG and/or elimination of plasma concentrations of DHPG and befloxatone after a single dose can be modeled using the Emax model with a mean EC50 of 4.75 ng/mL, and suggests the presence of a maximal response from the single dose. This model permits prediction of steady-state levels of DHPG.

Adult↗

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↗

PubMed1996

Single oral doses of amisulpride do not enhance the effects of alcohol on the performance and memory of healthy subjects.

OBJECTIVES: Amisulpride is a benzamide antipsychotic that binds selectively to dopamine D2- and D3-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a limited or negligible interaction with alcohol on human performance, amisulpride was studied for this potential. METHODS: In a randomised double-blind crossover study, 18 young, non-smoking men took single oral doses of placebo and amisulpride 50 mg and 200 mg, without and with ethanol (0.8 g. kg-1) taken 30 min later. Objective performance tests and self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after drug intake. Memory (immediate and delayed recall) was tested 2 h after dosing. Breath ethanol and the plasma concentrations of amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were used for statistical analyses; interactions were confirmed by factorial contrast ANOVA. RESULTS: Mean blood ethanol was 0.94, 0.62 and 0.26 g.1(-1) at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated driving, body sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosing. Amisulpride, 50 and 200 mg elevated plasma prolactin but had minimal or no effect on performance, attention and memory. The decreases in immediate free recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised ethanol in the digit copying test. Ethanol did not modify the effect of amisulpride on plasma prolactin, and the plasma concentrations of amisulpride were little changed by ethanol. CONCLUSIONS: Amisulpride in single oral doses of 50 and 200 mg did not interact significantly with the effects of high, moderate or low concentrations of ethanol on human skilled and cognitive performance. The drugs did interact pharmacokinetically.

Adult↗

PubMed1996

Pharmacoelectroencephalographic profile of befloxatone, a new reversible MAO-A inhibitor, in healthy subjects.

The pharmaco-EEG profile and the effects on P300 and CNV of befloxatone, a new selective and reversible MAO-A inhibitor, were assessed in a randomized, double-blind, placebo-controlled, 4-way crossover study. Twelve healthy young male volunteers were administered single doses of 2.5, 10 and 20 mg befloxatone and placebo separated by a 1-week washout. The EEG data were recorded before and at least 6 h after drug administration, by means of 28 leads allowing topographical analysis of the results. MAO inhibition, subjective effects and safety variables were also investigated. Statistical analysis was performed by means of the SDT method. Befloxatone induced dose-related EEG changes which occurred rapidly, peaked between 0.5 and 2 h and lasted at least until 6 h after drug administration. The EEG changes were characterized by an increase in absolute and/or relative alpha power, mainly alpha 1, after the 3 doses and a theta power increase after 10 and 20 mg only. These changes occurred mainly over the centroparietotemporal areas. Concerning the event-related potential, P300 latency of the auditory evoked potentials did not change. The P300 and CNV mean topographic amplitudes were decreased, between 0.5 and 2 h, after the two lowest doses for the P300 and the 3 doses for the CNV. After administration of 2.5, 10 and 20 mg, MAO inhibitions was shown by respectively 38, 76 and 81% reduction in plasma free 3, 4-dihydroxyphenylglycol reached after 2-4 h. Such a pharmaco-EEG profile, occurring at doses inducing MAO-A inhibition, is similar to those already described with nonsedative antidepressants.

Adult↗

PubMed1995

Pressor effect of oral tyramine during treatment with befloxatone, a new reversible monoamine oxidase-A inhibitor, in healthy subjects.

The interaction between tyramine and befloxatone, a new selective, reversible monoamine oxidase-A (MAO-A) inhibitor, was studied in a single-blind, parallel-group study in 30 healthy male volunteers whose fasting tyramine 30 dose (Tyr30) was 400 or 600 mg. Each subject completed a placebo run-in period followed by a befloxatone period. Befloxatone was given in repeated doses according to one of three regimens: befloxatone 20 mg once daily at the end of a meal rich in tyramine or befloxatone 10 or 20 mg twice daily 2 hours before a meal rich in tyramine. Subjects were given increasing daily doses of tyramine mixed with the meal, until a systolic blood pressure increase of at least 30 mm Hg was achieved (Tyr30). The mean Tyr30 decreased from 1220 mg (range, 600-1800 mg) during placebo to 290 mg (range, 150-500 mg) during befloxatone 20 mg once daily, 250 mg (range, 100-300) during befloxatone 10 mg twice daily, and 155 mg (range, 100-250 mg) during befloxatone 20 mg twice daily; corresponding to a potentiation factor of 5.2-, 6.5-, and 7.9-fold, respectively. The extent and the duration of the systolic blood pressure increase did not significantly differ between the placebo and the befloxatone regimens, except for a longer duration with the 20-mg twice daily regimen. These results are similar to those reported with the therapeutic dosage of other selective MAO-A inhibitors. They suggest that there would be little risk of hypertensive crisis in patients treated in clinical studies with befloxatone, and thus dietary restrictions appear to be unnecessary when the drug is given in a regimen of up to 20-mg once daily after meals.

Adult↗

PubMed1995

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.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗