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1.
J Ind Microbiol Biotechnol ; 29(2): 75-82, 2002 Aug.
Article in English | MEDLINE | ID: mdl-12161774

ABSTRACT

Bacteria isolated previously from ultrapure water (UPW) systems were examined for their ability to survive in UPW, with the ultimate goal of elucidating potential carbon and energy sources for the bacteria. Two strains of Ralstonia pickettii isolated from different areas within the UPW system (pretreatment and polishing loop, and referred to as strains 3A1 and MF254A, respectively) and a strain of Bradyrhizobium sp. were compared to increase our understanding of the fundamental behavior of bacteria contaminating UPW. R. pickettii (3A1) grew significantly slower in R2A medium, with a final cell yield much lower than the isolate from the polishing loop. In addition, R. pickettii MF254A showed a broader substrate range than either strain 3A1 or Bradyrhizobium sp. In UPW, there appears to be a threshold cell concentration (approximately 10(6) colony-forming units/ml), whereby the cell numbers remain constant for a prolonged period of 6 months or more. Below this concentration, rapid proliferation is observed until the threshold concentration is attained. Preliminary experiments suggested that nitrogen gas (frequently added to UPW storage tanks) may contribute to growth of Bradyrhizobium sp. Above the threshold concentration, the strain of Ralstonia sp. isolated from the polishing loop was capable of cryptic growth with heat-killed cells in UPW. However, cryptic growth was not observed when the cells supplied as nutrients were killed using UV254 light. Furthermore, cryptic growth did not appear to contribute significantly to proliferation of Bradyrhizobium sp. or Ralstonia sp. 3A1 (isolated from the pretreatment loop). We believe that cryptic growth may aid survival of the bacteria in UPW, but further experiments are warranted to prove this phenomenon conclusively.


Subject(s)
Gram-Negative Aerobic Rods and Cocci/isolation & purification , Gram-Negative Aerobic Rods and Cocci/metabolism , Water Microbiology , Water Purification , Colony Count, Microbial , Environment , Gram-Negative Aerobic Rods and Cocci/classification , Gram-Negative Aerobic Rods and Cocci/radiation effects , Hot Temperature , Time Factors , Ultraviolet Rays
2.
J Clin Psychopharmacol ; 20(5): 531-7, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11001237

ABSTRACT

This double-blind study compared mirtazapine's effects on alertness and sleep between parallel groups treated for 2 weeks according to a fixed regimen of 30 mg at bedtime (N = 69) and one that increased in dose from 15 to 30 mg at bedtime after the first week (N = 71). These patients with depression used an interactive telephone/computer system for daily alertness and sleep recordings on self-rating scales before and during treatment. Efficacy (17-item Hamilton Rating Scale for Depression [HAM-D], Clinical Global Impression Scale [CGI]) and safety assessments were made by participating psychiatrists. Both groups' alertness ratings were subnormal at baseline and even lower after the first dose. The ratings recovered after the second dose and increased progressively to levels 18% higher than those at baseline by the end of treatment. Patients receiving the fixed dose reported earlier sleep onset and longer duration. Similar mean changes in HAM-D scores (approximately -40%) and frequencies of CGI responders (>50%) occurred in both groups. The regimens were equally well tolerated. Somnolence, the most frequent side effect, was reported by only 10% of each group during the first week and by fewer patients during the second. Mirtazapine in fixed and ascending nocturnal dosing regimens was found to facilitate sleep, but it does not generally reduce daytime alertness. The fixed regimen seems preferable because of its greater effects on sleep.


Subject(s)
Antidepressive Agents, Tricyclic/therapeutic use , Attention/drug effects , Depressive Disorder/drug therapy , Depressive Disorder/psychology , Mianserin/analogs & derivatives , Sleep/drug effects , Affect , Antidepressive Agents, Tricyclic/administration & dosage , Dose-Response Relationship, Drug , Double-Blind Method , Humans , Mianserin/administration & dosage , Mianserin/therapeutic use , Mirtazapine , Psychiatric Status Rating Scales , Sleep Initiation and Maintenance Disorders/drug therapy , Sleep Initiation and Maintenance Disorders/psychology , Telephone
3.
Hum Psychopharmacol ; 15(7): 551-558, 2000 Oct.
Article in English | MEDLINE | ID: mdl-12404625

ABSTRACT

The objective of the current study was to assess the separate and combined effects of marijuana and alcohol on actual driving performance. Eighteen subjects were treated with drugs and placebo according to a balanced, 6-way, crossover design. On separate evenings they were given weight calibrated Delta(9)-tetrahydrocannabinol (THC) doses of 0, 100 and 200 &mgr;g/kg with and without an alcohol dose sufficient for achieving blood alcohol concentrations (BAC) of 0.04 g/dl while performing a Road Tracking and Car Following Test in normal traffic. Main outcome measures were standard deviation of lateral position (SDLP), time driven out of lane (TOL), reaction time (RT) and standard deviation of headway (SDH). Both THC doses alone, and alcohol alone, significantly impaired the subjects performances in both driving tests. Performance deficits were minor after alcohol and moderate after both THC doses. Combining THC with alcohol dramatically impaired driving performance. Alcohol combined with THC 100 and 200 &mgr;g/kg produced a rise in SDLP the equivalent of that associated with BAC=0.09 and 0.14 g/dl, respectively. Mean TOL rose exponentially with SDLP. Relative to placebo mean RT lengthened by 1.6 s under the combined influence of alcohol and THC 200 &mgr;g/kg. Changes in SDH ranged between 0.9 and 3.8 m. Low doses of THC moderately impair driving performance when given alone but severely impair driving performance in combination with a low dose of alcohol. Copyright 2000 John Wiley & Sons, Ltd.

4.
J Clin Psychopharmacol ; 19(3): 209-21, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10350027

ABSTRACT

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.


Subject(s)
Antipsychotic Agents/pharmacology , Basal Ganglia Diseases/chemically induced , Cognition/drug effects , Haloperidol/pharmacology , Psychomotor Performance/drug effects , Sulpiride/analogs & derivatives , Adult , Affective Disorders, Psychotic/chemically induced , Amisulpride , Antipsychotic Agents/adverse effects , Cross-Over Studies , Double-Blind Method , Female , Haloperidol/adverse effects , Humans , Male , Sulpiride/adverse effects , Sulpiride/pharmacology
5.
J Clin Psychopharmacol ; 18(3): 212-21, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9617980

ABSTRACT

Effects of venlafaxine, an antidepressant acting by selective serotonin and norepinephrine reuptake inhibition with a potency ratio of 5:1, were assessed in a standardized, actual driving test, a battery of psychomotor tests (Critical Flicker/Fusion Frequency, Critical Tracking, Divided Attention), and a 45-minute vigilance test (Mackworth Clock). Thirty-seven healthy volunteers, 22 of whom completed the study, received venlafaxine in fixed (37.5 mg twice a day) and incremental (37.5-75 mg twice a day) doses as well as mianserin (10-20 mg three times a day) and placebo according to a 4-period (15 days each), double-blind, crossover design. Testing occurred on days 1 and 7 and after dose increments, on days 8 and 15. Plasma concentrations of venlafaxine and its active metabolite were measured on test days for confirming compliance. Venlafaxine had no significant effect on the primary driving parameter (standard deviation of lateral position) and failed to impair psychomotor performance. Mianserin profoundly and consistently impaired driving and psychomotor performance. However, both drugs significantly impaired vigilance performance. Maximal effects occurred on day 1 with mianserin and similarly on day 7 with venlafaxine in both series. The increment in venlafaxine's dose on day 8 did not increase this effect. The drug's selectively impairing effect on vigilance is shared by other "serotonergic" anxiolytics and antidepressants, suggesting that interference with 5-HT transmission reduces arousal in particularly monotonous tasks or environments. This study concludes that venlafaxine does not generally affect driving ability and should be safe for use by patients who drive.


Subject(s)
Affect/drug effects , Antidepressive Agents, Second-Generation/pharmacology , Automobile Driving , Cyclohexanols/pharmacology , Psychomotor Performance/drug effects , Selective Serotonin Reuptake Inhibitors/pharmacology , Adult , Cyclohexanols/administration & dosage , Double-Blind Method , Female , Humans , Male , Mianserin/pharmacology , Venlafaxine Hydrochloride
6.
J Allergy Clin Immunol ; 101(3): 306-11, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9525444

ABSTRACT

BACKGROUND: Fexofenadine is the hydrochloride salt of terfenadine's active metabolite. OBJECTIVE: Fexofenadine's effects on performance were assessed in this study for the purpose of determining its safety of use by patients who engage in potentially dangerous activities, especially car driving. METHODS: Fexofenadine was administered in daily doses of 120 or 240 mg, each in single and divided units given over 5 days. Two milligrams of clemastine given twice daily and placebo were given in similar series. Twenty-four healthy volunteers (12 men, 12 women; age range, 21 to 45 years) participated in a double-blind six-way crossover study. Psychomotor tests (critical tracking, choice reaction time, and sustained attention) and a standardized actual driving test were undertaken between 1.5 to 4 hours after administration of the morning dose on days 1, 4, and 5 of each series. On day 5, subjects were challenged with a moderate alcohol dose before testing. RESULTS: Fexofenadine did not impair driving performance. On the contrary, driving performance was consistently better during twice daily treatment with 120 mg fexofenadine than during treatment with placebo, significantly so on day 4. Both of the 240 mg/day regimens significantly attenuated alcohol's adverse effect on driving on day 5. Effects in psychomotor tests were not significant, with the exception of the critical tracking test in which the first single doses of fexofenadine, 120 and 240 mg, had significantly impairing effects. CONCLUSION: It was concluded that fexofenadine has no effect on performance after being taken in the recommended dosage of 60 mg twice daily.


Subject(s)
Alcohol Drinking/adverse effects , Automobile Driving , Histamine Antagonists/adverse effects , Psychomotor Performance/drug effects , Terfenadine/analogs & derivatives , Adult , Anti-Allergic Agents/administration & dosage , Anti-Allergic Agents/therapeutic use , Clemastine/administration & dosage , Clemastine/therapeutic use , Cross-Over Studies , Double-Blind Method , Female , Histamine Antagonists/administration & dosage , Histamine Antagonists/therapeutic use , Humans , Male , Rhinitis, Allergic, Seasonal/drug therapy , Terfenadine/administration & dosage , Terfenadine/adverse effects , Terfenadine/therapeutic use
7.
Int Clin Psychopharmacol ; 12(3): 159-69, 1997 May.
Article in English | MEDLINE | ID: mdl-9248873

ABSTRACT

Parallel groups of depressed (DSM III-R) outpatients received moclobemide (n = 22) and fluoxetine (n = 19), double blind, for 6 weeks. Respective starting doses were 150 mg twice a day and 20 mg q.a.m. These could be doubled after 3 weeks for greater efficacy. Chronic users of benzodiazepine anxiolytics continued taking them as comedication. Therapeutic and side effects were assessed using conventional rating scales. Actual driving performance was assessed during the week before therapy and at 1, 3 and 6 weeks thereafter using a standardized test that measures standard deviation of lateral position (SDLP). Similar remissions in depressive symptoms and side effects occurred in both groups. Patients drove with normal and reliable (r = 0.87) SDLPs before treatments. Most continued to do so but a few drove with progressively rising SDLPs and the overall trends were significant in both groups (p < 0.03). A post-hoc multiple regression analysis was applied for identifying factors that correlated with SDLP in separate tests after the beginning of therapy. At 3 and 6 weeks there were significant (p < 0.03) relationships involving the same factor; patients who drove with progressively higher SDLPs appeared to be those using benzodiazepines that are metabolized by a P450 isozyme subject to inhibition by their particular antidepressant.


Subject(s)
Anti-Anxiety Agents/adverse effects , Antidepressive Agents/adverse effects , Automobile Driving/psychology , Cytochrome P-450 Enzyme System/metabolism , Depressive Disorder/enzymology , Depressive Disorder/psychology , Psychomotor Performance/drug effects , Adolescent , Adult , Aged , Anti-Anxiety Agents/blood , Anti-Anxiety Agents/therapeutic use , Antidepressive Agents/therapeutic use , Benzamides/adverse effects , Benzamides/therapeutic use , Benzodiazepines , Double-Blind Method , Drug Interactions , Drug Therapy, Combination , Female , Fluvoxamine/adverse effects , Fluvoxamine/therapeutic use , Humans , Male , Middle Aged , Moclobemide , Monoamine Oxidase Inhibitors/adverse effects , Monoamine Oxidase Inhibitors/therapeutic use , Psychiatric Status Rating Scales , Time Factors
8.
Br J Clin Pract ; 50(7): 381-5, 1996.
Article in English | MEDLINE | ID: mdl-9015911

ABSTRACT

Major depression can impair an individual's motivation to perform routine daily activities and cause a deterioration in cognitive and psychomotor function. Some antidepressants add to pathological dysfunction through unwanted side-effects. Although most patients eventually recover as a simultaneous consequence of tolerance and therapeutic response, some may not. Where side-effects continue to retard normal recovery they can be called behaviourally toxic, which can be classified as disruptive, inhibitory or provocative. Disruptive behavioural toxic effects are measured using either psychometric tests or simulations of real-life activities (for example, a driving test). There are no widely-accepted tests for inhibitory or provocative behavioural toxicity, and assessments of antidepressants are made on the basis of case studies. This review summarises the results of psychometric and real-life simulation tests and compares the effects of antidepressants on behaviour competence. The purpose is to identify those drugs that seem to be the most and least likely to produce behavioural toxicity.


Subject(s)
Antidepressive Agents/adverse effects , Behavior/drug effects , Activities of Daily Living , Humans , Psychological Tests
9.
Ann Allergy Asthma Immunol ; 76(3): 247-52, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8634878

ABSTRACT

OBJECTIVES: The purpose of this study was to test the hypothesis that learning ability is impaired in patients with seasonal allergic rhinitis relative to untreated individuals and to evaluate a combination compound (acrivastine 8 mg + pseudoephedrine 60 mg) for attenuation of the learning impairment in these patients. BACKGROUND: In a previous study employing the same method it was shown that young children (10 to 12 yrs) suffering from seasonal allergic rhinitis performed significantly worse on tests of learning and using knowledge after acute treatment with a sedating antihistamine (diphenhydramine 50 mg) or placebo as compared with nontreated healthy controls. This effect was partially reversed by treatment with loratadine. METHODS: Sixty-seven young adults suffering from seasonal allergic rhinitis and 28 matched controls were trained on didactic simulation for three consecutive days. Atopic subjects were treated differentially during training according to a double-blind, randomized, parallel group design with either diphenhydramine hydrochloride 50 mg, a combination compound (acrivastine 8 mg + pseudoephedrine 60 mg, A + P), or placebo, administered qd. After training, all atopic subjects were maintained on A + P treatment for 14 days at which time all groups returned for examination. RESULTS: Mean performance at the end of training was worse for all atopic subjects combined compared with normal subjects. Subjects treated with diphenhydramine performed significantly worse than either normals (P < .001) or those treated with A + P (P < .001). At the examination, the diphenhydramine group's performance differed significantly from those of the normal (P < .001) and A + P groups (P < .001). CONCLUSION: The study supports our previous finding that allergy symptoms reduce learning ability which is further reduced learning ability which is further reduced by diphenhydramine. Atopic subjects with allergies treated with acrivastine + pseudoephedrine learned as well as normal subjects.


Subject(s)
Diphenhydramine/adverse effects , Ephedrine/administration & dosage , Histamine H1 Antagonists/administration & dosage , Learning Disabilities/etiology , Rhinitis, Allergic, Seasonal/complications , Triprolidine/analogs & derivatives , Adolescent , Adult , Double-Blind Method , Drug Combinations , Female , Histamine H1 Antagonists/adverse effects , Humans , Learning/drug effects , Male , Memory/drug effects , Rhinitis, Allergic, Seasonal/drug therapy , Triprolidine/administration & dosage
10.
Eur J Clin Pharmacol ; 50(6): 475-82, 1996.
Article in English | MEDLINE | ID: mdl-8858275

ABSTRACT

OBJECTIVE: To determine whether mefloquine, a quinoline antimalarial drug, affects psychomotor and actual driving performance when given in prophylactic regimen, alone or in combination with alcohol. METHODS: Forty male and female volunteers were randomly assigned in equal numbers to two groups, and were treated double-blind for one month with mefloquine and placebo. The medication was taken in a 250 mg dose on the evenings of Days 1, 2, 3, 8, 15, 22 and 29. Testing was done on Days 4, 23 and 30, the latter after repeated doses of alcohol sufficient to sustain a blood concentration of about 0.35 mg.ml-1. Two real driving tests were used to measure prolonged (1 h) road tracking and car following performance. Critical Flicker/Fusion Frequency (CFF), critical instability tracking and body sway were also measured in the laboratory. RESULTS: Mefloquine caused no significant impairment in any test at any time relative to placebo. It significantly improved road tracking performance on Day 4. A significant interaction between prior treatment and alcohol was found in the body sway test, as the alcohol-induced change was less after mefloquine than placebo. The sensitivity of the driving test and the CFF test were shown by the significant overall effect of alcohol which did not discriminate between the two prior treatments. CONCLUSION: Mefloquine did not impair driving performance but rather improved it in the longer test, suggesting that the drug may possess psychostimulating properties.


Subject(s)
Antimalarials/adverse effects , Central Nervous System Depressants/adverse effects , Ethanol/adverse effects , Mefloquine/adverse effects , Psychomotor Performance/drug effects , Adult , Double-Blind Method , Drug Interactions , Ethanol/blood , Female , Humans , Male , Mefloquine/blood , Middle Aged
11.
J Psychopharmacol ; 10(4): 288-94, 1996 Jan.
Article in English | MEDLINE | ID: mdl-22302975

ABSTRACT

The effects of befloxatone (20 mg o.d. for 10 days) alone and in combination with ethanol on psychomotor performance, memory and mood were assessed in a randomized, double-blind, placebo controlled study. On treatment days 6, 8 and 10, subjects received 0.5 and 0.8 g/kg ethanol and ethanol placebo in randomly assigned, balanced orders, 2 h post-drug. Critical fusion frequency, choice reaction time, postural instability, critical tracking and mood were measured 1h before ethanol and 1, 3 and 5 h afterwards. Divided attention, sustained attention and memory (immediate and delayed recall) were also measured in single tests, 2.5-5 h post-ethanol.Ethanol's effects were generally significant when blood alcohol concentrations (BAC) after both doses were the highest; i.e. 0.48-0.67 and 0.96-1.10 mg/ml. Those effects were virtually gone after the subjects' mean BACs fell below 0.40 mg/ml. Befloxatone alone had no significant impairing effect in any test. Neither did it significantly interact with ethanol to cause any greater impairment than the latter alone. It was concluded that befloxatone does not potentiate the sedating and impairing effects of ethanol.

13.
Br J Clin Pharmacol ; 39(4): 397-404, 1995 Apr.
Article in English | MEDLINE | ID: mdl-7640146

ABSTRACT

1. The acute and subchronic effects of dothiepin 75-150 mg and fluoxetine 20 mg on critical fusion frequency (CFF), sustained attention and actual driving performance were compared with those of placebo in a double-blind, cross-over study involving 18 healthy volunteers. Drugs and placebo were administered for 22 days in evening doses. Fluoxetine doses were constant but dothiepin doses increased on the evening of day 8. Performance was assessed on days 1, 8 and 22 of each treatment series. Subjective sleep parameters and possible side effects were recorded on visual analogue scales on alternate treatment days. 2. Dothiepin reduced sustained attention on day 1 by 6.7% (95% confidence interval (C1): -12.0 to -1.3%) and CFF on day 22 by 1.1 (CI: -2.2 to -0.1) Hz. Fluoxetine reduced sustained attention days 1, 8 and 22 of treatment by 7.4, 6.7 and 6.5% respectively (CI: -11.3 to -3.6; -14.3 to -1.5 and -9.5 to -3.4). CFF decreased linearly over days during fluoxetine treatment and significantly differed from placebo on day 22 with 1.2 Hz (CI: -2.3 to -0.2). Neither drug significantly affected driving performance. Whilst receiving dothiepin, subjects complained of drowsiness on days 1-3 of treatment (mean rank 5.6; CI: 2.0 to 9.2) and slept 43 min longer (CI: 8.2 to 76.2).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Automobile Driving , Dothiepin/pharmacology , Fluoxetine/pharmacology , Psychomotor Performance/drug effects , Adult , Attention/drug effects , Chromatography, High Pressure Liquid , Cross-Over Studies , Dothiepin/adverse effects , Dothiepin/blood , Double-Blind Method , Female , Fluoxetine/adverse effects , Fluoxetine/blood , Humans , Male , Middle Aged , Multivariate Analysis , Sleep/drug effects , Surveys and Questionnaires
14.
Allergy ; 50(3): 234-42, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7677241

ABSTRACT

The review summarizes the major results of eight double-blind, placebo-controlled, volunteer studies undertaken by three independent institutions for showing the effects on actual driving performance of "sedating" and "nonsedating" antihistamines (respectively, triprolidine, diphenhydramine, clemastine and terfenadine, loratadine, cetirizine, acrivastine, mizolastine, and ebastine). A common, standardized test was used that measures driving impairment from vehicular "weaving" (i.e., standard deviation of lateral position (SDLP)). Logical relationships were found between impairment and dose, time after dosing, and repeated doses over 4-5 days. The newer drugs were generally less impairing, but differences existed among their effects, and none was unimpairing at doses 1-2x the currently recommended levels. One or possibly two of the newer drugs possessed both performance-enhancing and -impairing properties, depending on dose, suggesting two mechanisms of action.


Subject(s)
Automobile Driving , Histamine H1 Antagonists/adverse effects , Psychomotor Performance/drug effects , Benzimidazoles/administration & dosage , Benzimidazoles/adverse effects , Butyrophenones/administration & dosage , Butyrophenones/adverse effects , Cetirizine/administration & dosage , Cetirizine/adverse effects , Clemastine/administration & dosage , Clemastine/adverse effects , Diphenhydramine/administration & dosage , Diphenhydramine/adverse effects , Dose-Response Relationship, Drug , Histamine H1 Antagonists/administration & dosage , Humans , Loratadine/administration & dosage , Loratadine/adverse effects , Netherlands , Piperidines/administration & dosage , Piperidines/adverse effects , Terfenadine/administration & dosage , Terfenadine/adverse effects , Triprolidine/administration & dosage , Triprolidine/adverse effects , Triprolidine/analogs & derivatives
15.
Psychopharmacology (Berl) ; 118(1): 1-9, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7597114

ABSTRACT

This study was designed to confirm the hypothetical dose-dependent effect of alprazolam on memory and to compare its effects on tests measuring different aspects of cognitive and psychomotor functioning. A secondary purpose was to compare the sensitivity of newly developed telephone tests with a standard laboratory test of memory. Twenty healthy male volunteers (aged 18-35 years) participated in a five-way double-blind crossover design. Treatments were single oral doses of alprazolam (0.25, 0.5 and 1.0 mg), placebo and lorazepam 2.0 mg. The latter was included as an internal control for demonstrating sensitivity of the method. Lorazepam significantly impaired all performance measures except two: verbal fluency and accuracy of music recognition were insensitive to drug effects. Alprazolam had clear dose-dependent effects on different aspects of memory: 0.25 mg did not affect any parameter; 0.5 mg impaired performance in a Word Learning Test and a Spatial Memory Test and also psychomotor performance; 1.0 mg additionally impaired Syntactic Reasoning, Semantic Verification, and Critical Flicker Fusion performance. Alprazolam's effects were not selective for any of the cognitive functions as measured in this study. The telephone tests were clearly less sensitive than the standard test, though sufficient for showing significant effects of alprazolam 1 mg and lorazepam 2 mg.


Subject(s)
Alprazolam/administration & dosage , Lorazepam/administration & dosage , Memory/drug effects , Adolescent , Adult , Alprazolam/adverse effects , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Flicker Fusion/drug effects , Humans , Lorazepam/adverse effects , Male , Mental Processes/drug effects , Psychomotor Performance/drug effects , Reaction Time/drug effects , Space Perception/drug effects , Verbal Learning/drug effects
16.
Eur Neuropsychopharmacol ; 5(1): 35-42, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7613099

ABSTRACT

The effects of paroxetine (20 and 40 mg/day) and amitriptyline (75 mg/day, used as an active control) on car driving and psychomotor function were compared with those of placebo in a double-blind, crossover study employing 16 healthy subjects. Performance testing occurred on the first and last day of each 8-day treatment series. Side-effects, sleep duration and sleep quality were rated daily. Amitriptyline produced severe drowsiness and strikingly impaired performance on nearly every test on the first day but its effects were practically gone after 1 week of treatment. Paroxetine 20 mg, the usual antidepressant dose, had no effect on performance. Paroxetine 40 mg did not affect road tracking but slightly impaired performance in some psychomotor tests in a persistent manner. Paroxetine had no effect on sleep following the 20 mg dose but reduced quality following the 40 mg dose. Side-effects that the administered drugs have in common were milder during paroxetine than amitriptyline treatment. However, some dose-related side-effects (e.g. nausea and delayed ejaculation) were only reported during paroxetine treatment.


Subject(s)
Paroxetine/pharmacology , Psychomotor Performance/drug effects , Adult , Amitriptyline/pharmacology , Humans , Male , Paroxetine/adverse effects , Psychiatric Status Rating Scales , Sleep , Surveys and Questionnaires , Time Factors
17.
Neuropsychobiology ; 31(2): 81-8, 1995.
Article in English | MEDLINE | ID: mdl-7760989

ABSTRACT

Effects of benzodiazepine (diazepam, lorazepam) and benzodiazepine-like anxiolytics (alpidem, suriclone) and a 5-HT-3 antagonist (ondansetron) on actual driving performance were measured in three double-blind, placebo-controlled studies. Subjects were healthy volunteers in two and anxious patients in the third. Treatments lasted for 8 days. Standardized testing occurred within the first full day and on the last day of treatment. No important differences existed between volunteers' and patients' baseline and/or placebo performances and both groups responded similarly to comparable drugs/doses. Benzodiazepine and benzodiazepine-like anxiolytics produced marked and pervasive driving impairment, which lasted throughout treatment; but ondansetron, none.


Subject(s)
Anti-Anxiety Agents/adverse effects , Anxiety Disorders/drug therapy , Attention/drug effects , Automobile Driving , Psychomotor Performance/drug effects , Anti-Anxiety Agents/therapeutic use , Anxiety Disorders/psychology , Automobile Driving/psychology , Cross-Over Studies , Diazepam/adverse effects , Diazepam/therapeutic use , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Humans , Imidazoles/adverse effects , Imidazoles/therapeutic use , Lorazepam/adverse effects , Lorazepam/therapeutic use , Middle Aged , Naphthyridines , Ondansetron/adverse effects , Ondansetron/therapeutic use , Piperazines/adverse effects , Piperazines/therapeutic use , Pyridines/adverse effects , Pyridines/therapeutic use , Sulfur Compounds
18.
Eur J Clin Pharmacol ; 47(3): 253-9, 1994.
Article in English | MEDLINE | ID: mdl-7867678

ABSTRACT

The acute effect of doses of mizolastine 5, 10, 20 and 40 mg, an active control (clemastine 2 mg) and placebo on actual car driving and psychomotor performance have been compared. Twenty four healthy volunteers were treated according to a double-blind, 6-way cross-over design. In the driving test, lasting about 1 h, lateral position control and speed were continuously measured; the psychomotor test battery, lasting 50 min, comprised critical flicker-fusion frequency, critical instability tracking, divided attention, memory search and choice reaction time, and vigilance studies; and mood changes and possible adverse-effects were rated on visual analogue scales. The results showed a dose-response relationship: mizolastine 40 and 20 mg impaired driving and psychomotor performance. The effect of mizolastine 40 mg on driving was strongly correlated with that of clemastine (r = 0.78) and was comparable to the effect of a blood ethanol level of 0.8 mg.ml-1. Mizolastine 5 mg and 10 mg did not have a significant effect on driving performance and psychomotor tests. It was concluded that at a 10 mg dose of mizolastine, the therapeutic dose, it could be considered a safe anti-histamine, although individual adverse reactions cannot be completely ruled out.


Subject(s)
Automobile Driving , Benzimidazoles/pharmacology , Clemastine/pharmacology , Histamine H1 Antagonists/pharmacology , Psychomotor Performance/drug effects , Adult , Affect/drug effects , Behavior/drug effects , Benzimidazoles/adverse effects , Clemastine/adverse effects , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Histamine H1 Antagonists/adverse effects , Humans , Male , Psychometrics , Reaction Time/drug effects , Sensitivity and Specificity
19.
Eur J Clin Pharmacol ; 47(3): 261-6, 1994.
Article in English | MEDLINE | ID: mdl-7867679

ABSTRACT

The study was conducted according to a nine-way, observer- and subject-blind, cross-over design. Its purpose was to compare the single-dose effects of the following drugs on driving performance: acrivastine (8, 16 and 24 mg); the combination of acrivastine (8 mg) with pseudoephedrine (60 mg); terfenadine (60, 120 and 180 mg); diphenhydramine-HCl (50 mg); and placebo. The subjects were 18 healthy female volunteers. Drug effects were assessed in two repetitions of two driving tests (highway driving and car-following) after each treatment. Acrivastine's impairing effects in both driving tests were similarly dose-related. The 8-mg dose had a small, but significant, effect on highway driving in the first trial. The 16-mg and 24-mg doses significantly impaired driving in both tests during the first trial and the 24-mg dose did so again during the second trial. Neither the combination of acrivastine with pseudoephedrine nor terfenadine caused any significant impairment of performance. Diphenhydramine significantly impaired driving in both tests during every trial. In conclusion, the normal therapeutic dose of acrivastine (8 mg) had little effect on driving performance, and virtually none when that dose was given in combination with pseudoephedrine (60 mg). Higher doses of acrivastine severely impaired driving performance. Terfenadine had no significant effect on driving performance after any dose while diphenhydramine strongly impaired every important driving parameter.


Subject(s)
Automobile Driving , Diphenhydramine/pharmacology , Diphenhydramine/pharmacokinetics , Terfenadine/pharmacology , Terfenadine/pharmacokinetics , Triprolidine/analogs & derivatives , Administration, Oral , Adult , Cross-Over Studies , Diphenhydramine/adverse effects , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Ephedrine/pharmacology , Ephedrine/urine , Female , Humans , Infant, Newborn , Middle Aged , Single-Blind Method , Terfenadine/adverse effects , Triprolidine/adverse effects , Triprolidine/pharmacokinetics , Triprolidine/pharmacology
20.
Clin Neuropharmacol ; 17 Suppl 1: S9-18, 1994.
Article in English | MEDLINE | ID: mdl-7954488

ABSTRACT

Results from two separate studies were combined to compare the acute and subchronic effects of two monoamine oxidase-A (MAO-A) inhibitors, moclobemide and brofaromine, on actual driving performance and sleep. Both studies were conducted according to a double-blind, crossover design involving 18 patients receiving moclobemide and 16 patients receiving brofaromine. Patients were administered either moclobemide 200 mg b.i.d., mianserin 10 mg. t.i.d., and placebo (study 1), or brofaromine 50 and 75 mg b.i.d., doxepin 25 mg t.i.d., and placebo (study 2) for 8 consecutive days. A standardized driving test was conducted on day 1 and day 8 of treatment. Daily logs of estimated sleep duration and quality were obtained. Neither moclobemide nor brofaromine impaired driving performance. Some indication, although statistically not significant, was found that moclobemide improved driving performance on day 1. Brofaromine 75 mg significantly improved driving performance on day 8 of treatment. No significant difference between the effects of both drugs was found in a cross-study comparison. Moclobemide did not affect any sleep parameter, whereas brofaromine shortened sleep duration and decreased sleep quality. On day 1, mianserin and doxepin impaired driving. Impairment dissipated after 8 days of treatment with doxepine but not during treatment with mianserin. Sleep duration was prolonged during treatment with both drugs, whereas sleep quality remained unaffected. It is concluded that both MAO-A inhibitors are safe drugs with respect to driving.


Subject(s)
Automobile Driving , Benzamides/adverse effects , Monoamine Oxidase Inhibitors/adverse effects , Piperidines/adverse effects , Psychomotor Performance/drug effects , Sleep/drug effects , Adult , Cross-Over Studies , Double-Blind Method , Doxepin/adverse effects , Female , Humans , Male , Mianserin/adverse effects , Middle Aged , Moclobemide , Multivariate Analysis
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