What makes lorazepam different from other benzodiazepines?
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Afferent Pathways↗
Biomedical subjects
S Pompéia
Publications and source records attributed to S Pompéia.
Zolpidem and memory: a study using the process-dissociation procedure.
RATIONALE: There is a dearth of studies which have employed sophisticated paradigms to investigate the effects of zolpidem on memory. OBJECTIVES: To explore anterograde cognitive deficits induced by acute oral doses of zolpidem by means of the process-dissociation procedure (PDP). METHODS: The present study followed a placebo-controlled, double-blind, parallel-group design. Young, healthy females were randomly allocated to one of three treatments with 12 subjects each: placebo, 5 mg and 10 mg zolpidem. Two word-stem completion tasks were carried out close to theoretical peak-plasma concentration: a) direct inclusion task with cued recall, in which participants had to try to use words seen at study to complete stems; and b) direct exclusion task, in which words seen at study were to be avoided as completions. The PDP was applied to the results in these tasks to yield indices of explicit/controlled (C) and implicit/automatic (A) memory. Classical psychometric tests were also carried out. RESULTS: Zolpidem 10 mg led to cognitive effects similar to benzodiazepines (except for the atypical lorazepam), including impairment of exclusion, but not inclusion-task performance. Results of the application of the PDP were inconclusive but concurred with the pattern established in previously published work on benzodiazepine effects, i.e. that zolpidem (10 mg) impaired C. CONCLUSIONS: Zolpidem leads to cognitive effects similar to most benzodiazepines. Although the application of PDP in drug studies may be counterproductive in view of methodological difficulties that are discussed, the pattern of effects on the stem-completion tasks involved in this paradigm is potentially useful in the investigation of cognitive effects of psychoactive drugs.
Administration, Oral↗
Lorazepam should no longer be used as a prototypical benzodiazepine.
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Animals↗
Stem-completion tasks (indirect, direct inclusion and exclusion) are differently affected by equipotent doses of lorazepam and flunitrazepam.
This study was designed to explore the effects on performance in stem-completion tasks of two benzodiazepines (BZ) in equipotent doses: lorazepam, a drug that atypically disrupts perceptual priming, and flunitrazepam, a compound with standard BZ effects. The study followed a placebo-controlled, double-blind, parallel-group design. Thirty-six young and healthy subjects carried out three completion tasks at theoretical peak-plasma concentrations of drugs: (a) indirect tasks, in which the subjects were instructed to complete stems with the first word that came to mind; (b) direct inclusion tasks/cued recall, in which the participants had to try to use words seen at study as completions; and (c) direct exclusion tasks, in which words seen at study were to be avoided. The PDP was applied to the results in the inclusion and exclusion tasks, to obtain indices of explicit/controlled (C) and implicit/automatic (A) memory. The C index was lowered by both BZs and A was equivalent in all treatments, confirming the general amnestic action of BZs. However, lorazepam led to decreases in completions in the indirect and inclusion tasks, while flunitrazepam impaired performance in the exclusion task. The qualitative differences between the drugs in their effects on performance suggest that these BZs may lead to differences in response bias.
Administration, Oral↗
Lorazepam induces an atypical dissociation of visual and auditory event-related potentials.
Lorazepam has been reported to atypically disrupt visual processing compared to other benzodiazepines (BZs), but it is not known to what extent this effect extends to impairment in other modalities. Our objective was to compare the effects of lorazepam with those of flunitrazepam, a BZ with standard effects, on visual and auditory event-related potentials (ERPs) using the same paradigm. The study followed a placebo-controlled, double-blind, parallel group-design and involved single oral doses of lorazepam (2.0 mg), flunitrazepam (1.2 mg) and placebo. Thirty-six young, healthy subjects completed a test battery before and after treatment including classic behavioural tests, visual and auditory ERPs. Both drugs led to comparable alterations on behavioural tests and double-dissociations were found, indicating that the doses used were equipotent: lorazepam was more deleterious than flunitrazepam and placebo in fragmented shape identification, while simple reaction times were prolonged for flunitrazepam in comparison to lorazepam and placebo. Effects on P3 latencies were also distinct: alterations in both modalities for flunitrazepam were equivalent and greater than placebo's. In contrast, lorazepam at the frontal and central electrode sites led to greater changes in visual than in auditory latency, and also to longer visual latencies than flunitrazepam and placebo, but lorazepam's auditory latency effects were only different to placebo's at the parietal electrode site. Peripheral visual changes were not responsible for these effects. Differences in the impairment profile between equipotent doses of lorazepam and flunitrazepam suggests that lorazepam induces atypical central visual processing changes.
Adolescent↗
Verbal fluency facilitated by the cholinergic blocker, scopolamine.
This study was designed to explore putative facilitatory effects of low doses of scopolamine (SP) on phonemic (letter) and semantic (category) verbal fluency. A double-blind, parallel-group design was used with 36 subjects who completed a test battery before and 2 h after 0.6 mg or 1.2 mg of SP or placebo. Fluency measures included total number of words generated, clustering (the production of words within semantic or phonemic subcategories) and switching (the ability to shift efficiently to new subcategories). Low doses of scopolamine increased phonemic fluency, as has been shown previously. Semantic fluency was not increased by SP, although subjects treated with 1.2 mg of SP generated higher-frequency words. SP did not affect clustering or switching. It is suggested that phonemic and semantic fluency reflect distinct cognitive processes.
Adolescent↗
A set of 400 pictures standardised for Portuguese: norms for name agreement, familiarity and visual complexity for children and adults.
The present article provides normative measures for 400 pictured objects (Cycowicz et al., 1997) viewed by Portuguese speaking Brazilian University students and 5-7 year-old children. Name agreement, familiarity and visual complexity ratings were obtained. These variables have been shown to be important for the selection of adequate stimuli for cognitive studies. Children's name agreement was lower than that of adults. The children also failed to provide adequate modal names for 103 concepts, rated drawings as less familiar and less complex, and chose shorter names for pictures. The differences in ratings between adults and children were higher than those observed in the literature employing smaller picture sets. The pattern of correlations among measures observed in the present study was consistent with previous reports, supporting the usefulness of the 400 picture set as a tool for cognitive research in different cultures and ages.
Adult↗
A double-dissociation of behavioural and event-related potential effects of two benzodiazepines with similar potencies.
This study was designed to explore the role of benzodiazepine affinity to benzodiazepine binding site on acute psychomotor, subjective and memory effects, as well as auditory Event Related Potential (ERP) latencies, in healthy volunteers. Two benzodiazepines with similar affinity to benzodiazepine binding sites, or potency, were compared: the atypical compound lorazepam (2.0 mg), which has been reported to impair priming, and a standard benzodiazepine, flunitrazepam (0.6 mg, 0.8 mg, 1.0 mg). The study followed a placebo-controlled, double-blind, parallel-group design. Sixty subjects completed a test battery before treatment and at theoretical peak plasma concentration of drugs. Lorazepam and 1.0 mg of flunitrazepam led to comparable alterations on psychomotor, subjective and auditory episodic memory measures. A double-dissociation was found for lorazepam and the equipotent dose of flunitrazepam (1.0 mg): lorazepam was more deleterious than flunitrazepam in time taken to identify fragmented shapes. Lorazepam also impaired direct and indirect stem-completion in comparison to placebo, but this effect was abolished when time to identify shapes was used as a covariate. By contrast, 1.0 mg of flunitrazepam prolonged auditory ERP latencies to a greater extent than lorazepam. High affinity to the benzodiazepine binding sites does not seem to explain the consistent lorazepam-induced impairment of indirect stem-completion. Differences in impairment profile between the benzodiazepines employed may relate to the modality (visual or not) of the tasks used.
Adolescent↗
Preliminary adaptation into Portuguese of a standardised picture set for the use in research and neuropsychological assessment.
Pictorial stimuli and words have been widely used to evaluate mnemonic processes in clinical settings, neuropsychological investigations, as well as in studies on the mechanisms underlying the phenomena of memory. However, there seem to be few studies of standardisation of pictures for research in this field. The present paper aimed at adapting the use of a set of pictures standardised for English speaking subjects for Portuguese speakers. Name agreement of 150 pictures was assessed in 100 high-school students. Ninety pictures were found to present the same name for over 90 subjects. Results yield data that may help create more controlled tests for the study of memory for pictorial stimuli in Brazil.
Adolescent↗
Benzodiazepine effects on memory tests: dependence on retrieval cues?
Acute effects of oral flunitrazepam (0.5 and 1 mg), nitrazepam (5 and 10 mg) and placebo were assessed on direct (free recall of words and prose, stem-cued recall) and indirect (stem and fragment completion) memory tasks. Fifty health volunteers took part in this double-blind, independent group study. The relative effects of the two benzodiazepines (BZs) on memory revealed a different pattern from their effects on alertness, indicating that their amnesic effects are not totally secondary to their sedative effects. The higher dose of flunitrazepam impaired free recall of words and prose but not cued recall, while neither drug affected the two indirect tasks. Differences in drug effects on the direct and indirect memory tasks were discussed in terms of resource demands of the various tests. We conclude that whether BZs impair performance on memory tasks depends more on the cues given at retrieval than the retrieval instructions (direct/indirect). The implications for this in terms of BZ amnestic effects are drawn out for contextual encoding deficits induced by BZs.
Administration, Oral↗
Scores of Brazilian University students on the Beck Depression and the State Trait Anxiety Inventories.
The profiles of the Beck Depression Inventory and State-Trait Anxiety Inventory scores were obtained for a sample of Brazilian university students and compared with those of other studies. Subjects were 270 students from various universities in São Paulo, age 23.8 yr. (SD=6.7 yr.). The mean Beck score for the total sample was 8.5 (SD=7.0); according to the cut-off score of 16, 86.9% were considered normal, 7.5% had scores compatible with dysphoria, and 5.6% had scores indicative of depression. The mean State-Trait Anxiety score for the total sample was 40.7 (SD=8.6). Considering one standard deviation as the threshold point, 17.8% published data indicated that the Portugese versions of the questionnaires are equivalent to original versions.
Adult↗
Differential acute psychomotor and cognitive effects of diazepam on long-term benzodiazepine users.
The aim of this study is to determine whether long-term use (5-20 years) of therapeutic doses of diazepam (5-20 mg/day) in anxious patients (n = 28) is associated with tolerance to its psychomotor and cognitive effects. Patients were tested at baseline, before and after a 10 mg oral dose of diazepam during chronic use, and at 3 weeks and 10 months after benzodiazepine (BZ) discontinuation. The effects of a single i.v. dose of flumazenil (1 mg administered 5 days before baseline) on reversing tolerance were also assessed. No acute effect of diazepam was observed on the psychomotor performance of patients both under BZ treatment and after short- and long-term discontinuation, suggesting persistence of tolerance. In contrast, acute effects of diazepam were observed in memory measures at all times. Given subjects' very prolonged BZ use, it is possible to predict that tolerance to the memory effects never fully develops. Flumazenil administration did not reverse tolerance. This suggests that neuroadaptative mechanisms, other than benzodiazepine receptor set-point shift, occur after long-term use.
Adult↗