Biomedical subjects

H V Curran

Publications and source records attributed to H V Curran.

At least 37 records · Page 2Linked to original sources

PubMed1998

The influence of alcoholism and cirrhosis on benzodiazepine receptor function.

In a previous study we reported that the affinity of the platelet benzodiazepine receptor was greater in alcoholic cirrhotic patients compared with normal controls and that there were detectable ligands for the neuronal benzodiazepine receptor in plasma from both alcoholic and nonalcoholic cirrhotic patients. The aim of the present study was to assess the separate contributions of alcoholism and cirrhosis to the presence of ligands in plasma for the neuronal and peripheral benzodiazepine receptors and to changes in peripheral benzodiazepine receptor binding in platelets. These parameters were measured in 10 alcoholic cirrhotics, 9 nonalcoholic cirrhotics, 7 alcoholics with a normal liver function, and 15 nonalcoholic subjects and normal liver function. Both groups of alcoholics had been abstinent for several months and the nonalcoholic groups had abstained for 24 h before the study. The concentration of ligands for the peripheral benzodiazepine receptor were significantly higher in both cirrhotic groups compared with the other two groups, suggesting that cirrhosis was responsible for this accumulation. Furthermore, the cirrhotic patients with detectable concentrations of these ligands had significantly poorer episodic memory than those without ligands. However, the presence of ligands for the peripheral benzodiazepine receptor did not correlate with the change in receptor affinity, which was increased in the alcoholic cirrhotic group compared with all other groups. Neither cirrhosis nor alcoholism altered the peripheral benzodiazepine receptor number. The cirrhotic patients with detectable ligands for the neuronal benzodiazepine receptor showed psychomotor slowing and executive dysfunction. The results suggest that the ligands for the peripheral benzodiazepine receptor may contribute to some of the cognitive deficits seen in hepatic encephalopathy, but are not responsible for the receptor affinity change seen in the alcoholic cirrhotics. This affinity change is not solely due to the effects of alcohol and could possibly serve as a marker for those at risk for developing alcoholic cirrhosis.

Adult↗

PubMed1997

Mood and cognitive effects of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy'): week-end 'high' followed by mid-week low.

AIMS: Recreational use of +/-3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') is widespread. The present study aimed to examine both the acute and residual effects of this drug on users' mood and cognitive function. DESIGN AND PARTICIPANTS: A parallel group design was used to compare 12 participants who reported having taken MDMA with 12 participants who reported having consumed only alcohol, on the relevant night (day 1). These same participants were then re-assessed the following day (day 2) and again mid-week (day 5). FINDINGS: Acute effects of MDMA broadly replicated previous findings. MDMA users rated elevated mood on day 1 but significantly low mood on day 5, at which point some participants scored within the range for clinical depression. In contrast, the alcohol group showed less pronounced changes, which followed a U-shaped curve over days with the lowest point being day 2. The MDMA group also showed significant impairments on an attentional/working memory task, compared with alcohol users. CONCLUSIONS: Weekend use of MDMA may lead to depressed mood mid-week. Possible mechanisms underlying the findings are discussed in terms of temporary depletion of serotonin, serotonergic neurotoxity and psychological aspects of mood change.

Adult↗

PubMed1996

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↗

PubMed1996

Cognitive impairments of alcoholic cirrhotic patients: correlation with endogenous benzodiazepine receptor ligands and increased affinity of platelet receptors.

OBJECTIVES: To determine whether differences in cognitive function between alcoholic and non-alcoholic cirrhotic patients relate to differences in endogenous ligands for the benzodiazepine receptor and/or benzodiazepine binding. METHODS: Seventeen grade-I hepatic encephalopathic patients (nine alcoholic, eight non-alcoholic) were compared with 10 matched controls on plasma concentrations of endogenous ligands for the neuronal benzodiazepine receptor, benzodiazepine binding in platelets, and performance on tests of cognitive function. RESULTS: Both groups of patients were impaired on verbal recall and on reaction time tasks compared with controls; alcoholic patients were also impaired on Reitan's trails test and digit cancellation. Four of the 17 patients had detectable concentrations of endogenous benzodiazepine ligands and they were more impaired than other patients on trails and cancellation tests. The groups did not differ in the density of benzodiazepine platelet receptors, but receptor affinity was higher in alcoholic patients than in controls; furthermore, receptor affinity correlated with the time to complete the cancellation task and with reaction time. CONCLUSION: Alcoholic cirrhotic patients may have enhanced concentrations of ligands for neuronal and peripheral benzodiazepine receptors and these may contribute to cognitive impairments in these patients.

Adult↗

PubMed1995

Behavioural aggression in panic disorder after 8 weeks' treatment with alprazolam.

23 patients with a diagnosis of panic disorder with agoraphobia were randomly assigned to 8 weeks' treatment with alprazolam or placebo. They filled in self-ratings before and after treatment and competed on a competitive reaction time task, designed to measure behavioural aggression, after 8 weeks' treatment. Patients taking both alprazolam and placebo rated decreased anxiety after 8 weeks' treatment but those on alprazolam also tended to report less hostility. On the behavioural task, patients on alprazolam behaved more aggressively in response to provocation. This is the first study to confirm clinical reports of benzodiazepine-induced dyscontrol on an objective laboratory measure. It is important that it is followed up in a larger group of patients.

Adult↗

PubMed1995

Psychopharmacological analysis of implicit and explicit memory: a study with lorazepam and the benzodiazepine antagonist flumazenil.

Recent studies have suggested that the benzodiazepine (BZ) lorazepam (LZ) differs from other BZs in its impairing effects on implicit memory tasks. The present study was designed to assess whether this atypical effect withstood the experimental rigour of Schacter's retrieval intentionality criterion and further, whether it could be reversed by the BZ antagonist, flumazenil (FL). The separate and combined effects of LZ, FL and placebo (PL) were assessed on indices of memory, sedation, and attention in 48 healthy volunteers. LZ disrupted performance on both explicit and implicit memory tasks, induced motor sedation and impaired focussed attention. Fl attenuated LZ-induced attentional deficits but did not affect motor sedation. FL also attenuated LZ-induced impairment on the implicit retrieval task. On the explicit retrieval task FL attenuated LZ-induced impairment for words which had been deeply processed at study but not words which had been shallowly processed. A subsequent recognition test showed LZ impaired recognition memory only when accompanied by recollective experience and flumazenil again attenuated this effect. FL itself lowered performance on several measures, reflecting intrinsic activity of this "antagonist". Assessment of the relationship between the mnestic and other effects of the drugs suggested that attentional effects contribute to, but do not explain, effects on implicit memory tasks. These results imply that the apparent atypical effects of LZ on implicit memory tasks are mediated by the same BZ receptor complex as mediates LZ's other effects.

Adolescent↗

PubMed1995

Encoding, remembering and awareness in lorazepam-induced amnesia.

The effects of lorazepam (1,2 mg) and placebo on encoding, remembering and awareness were assessed in a study with 54 healthy volunteers. All subjects studied stimulus materials in a levels of processing (L-o-p) task. Half the subjects were assessed on an explicit memory task of word recognition and the other half were given an implicit memory task of word-stem completion. Following the implicit task, awareness of retrieval was further investigated by questions and by subjects' recollective experience in recognising the actual words they had completed from stems. L-o-p effects and marked lorazepam-induced impairments were found in the implicit task of word-stem completion although the interaction between L-o-p and drug effects emerged only as a trend in the data. Lorazepam-induced impairments on stem-completion may then be explained at least in part as being due to contamination by explicit retrieval processes, but we cannot rule out the possible role of drug effects on perceptual processes at encoding. Results from responses to "awareness" questions and from analysis of subsequent recollective experience indicated that subjects were not aware of using explicit retrieval during the implicit task. Results also replicated previous findings showing that both lorazepam and L-o-p independently affect performance in an explicit memory task of word recognition. Thus drug-induced deficits at encoding persist regardless of the level at which information is initially processed.

Adult↗

PubMed1994

Pharmacological models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on word valence ratings, priming and recall.

The effects of scopolamine (0.3, 0.6 mg IM) lorazepam (2 mg oral) and placebo on word valence ratings, priming and word recall were assessed in a double-blind independent group design with 36 subjects. Subjects given active drugs rated words as having more of an affective load than subjects given placebo. Priming, as assessed in a word-stem completion task, was not significantly affected by any treatment. Word recall showed some impairment following all active treatments. Performance on the stem completion task was unrelated to subjectively rated sedation but did not relate to word-valence ratings in different ways across drug treatments. Performance on the recall task was unrelated to valence ratings but did relate to the sedative effects on lorazepam. Implications are drawn out for pharmacological models of memory dysfunction.

Adult↗

PubMed1994

Flumazenil has an anxiolytic effect in simulated stress.

This study was designed to test whether or not flumazenil (1 mg IV) would change levels of anxiety induced by simulation of public speaking (PSS). Forty normal volunteers were randomly allocated in a parallel groups design to treatment with flumazenil or placebo (double-blind) and one of two stress conditions (PSS/control task). PSS increased anxiety and flumazenil antagonized this effect. The anxiolytic activity of flumazenil was particularly strong on anticipatory anxiety measures. The results were discussed in terms of the involvement of endogenous benzodiazepine-type ligands in the regulation of the human response to stress.

Adolescent↗

PubMed1994

Memory functions, alprazolam and exposure therapy: a controlled longitudinal study of agoraphobia with panic disorder.

Benzodiazepines (BZs) produce transient anterograde amnesia when given to normal subjects. The present longitudinal study assessed whether BZs impair memory functions in a clinically anxious group. Eighty-two agoraphobics with panic disorder were randomly allocated to one of four treatment groups resulting from a combination of two drug treatments (alprazolam or placebo) and two psychological treatments (exposure or relaxation). Of these, 38 subjects were assessed on a range of objective and subjective indices of memory and mood at three time points: before treatment, after 8 weeks of treatment and again at 24 weeks when patients had been free of medication from 5-8 weeks. Alprazolam produced pronounced impairments on a word recall task. At the 24-week medication-free follow-up, alprazolam patients were still impaired on the task compared with placebo patients. Alprazolam did not impair performance on an implicit memory task and did not affect digit span. Differences between psychological treatments emerged mainly in subjective memory effects. Findings are discussed in terms of the specificity of BZ-induced amnesia and differential tolerance to the varying effects of BZs. Implications are drawn out for the patient's ability to function optimally in daily life while taking alprazolam.

Adult↗

PubMed1993

The effects of single doses of CL284,846, lorazepam, and placebo on psychomotor and memory function in normal male volunteers.

The effects of single doses of CL284,846 (20 mg), lorazepam (2 mg) and placebo on psychomotor performance, memory function and subjective feelings were assessed in 12 normal, healthy male volunteers. Each subject received each treatment in balanced order and a minimum of 6 days was left between treatments. The subjects performance on a comprehensive battery of tests of psychomotor performance, memory function and subjective ratings was assessed pre-treatment and at 1, 3 and 5 h post-treatment. In general, the effects of CL284,846 on memory were similar to those of lorazepam at 1 h post-treatment but, recovery was rapid with CL284,846. Impairments induced by lorazepam persisted throughout the post-drug testing sessions. This pattern of effects was repeated across most of the variables tested. However, at 1 h, CL284,846 produced less marked psychomotor impairment than lorazepam. The results of this study suggest that CL284,846 is a safe, rapid acting and effective sedative with some clear advantages over lorazepam with respect to unwanted cognitive and psychomotor impairments.

Acetamides↗

PubMed1993

Effects of lorazepam upon recollective experience in recognition memory.

The effects of lorazepam (2 mg) and placebo upon recognition memory with and without conscious recollection were assessed in a cross-over study with normal volunteers. When recognising a word from study lists presented before and 1, 3 and 5 h after drug administration, subjects were required to indicate whether they could consciously recollect the word's prior occurrence or recognised it on the basis of "knowing"; in the absence of conscious recollection. Lorazepam only impaired word recognition which was accompanied by conscious recollection, and further, the level of this impairment correlated significantly with each of three different indices of subjects' arousal at the time of presentation of each list. Recognition in the absence of conscious recollection was not impaired but somewhat heightened by lorazepam, and these effects did not significantly relate to any index of arousal. These findings are interpreted as providing further support for the notion that recognition entails two distinct components, one based on contextual and associative information and related to conscious recollection, the other possibly based on a "traceless" perceptual or semantic memory system and related to feelings of knowing in the absence of conscious recollection. Implications are drawn for a contextual-encoding/retrieval account of lorazepam-induced amnesia.

Adult↗

PubMed1993

Memory and psychomotor effects of oxcarbazepine in healthy human volunteers.

Cognitive and psychomotor impairments can be unwanted adverse effects of antiepileptic drugs. The present double-blind, cross-over study with healthy volunteers was designed to assess the effects of two doses of oxcarbazepine (OXCZ) (150 mg b.i.d.; 300 mg b.i.d.) and a placebo, each given over a two week period. Twelve subjects completed a battery of tests before and 4 h after morning doses on days 1, 8 and 15. Results of objective tests indicated that OXCZ improved performance on a focussed attention task and increased manual writing speed. Subjective ratings showed OXCZ increased feelings of altertness, clear-headedness and quickwittedness. OXCZ had no effect on the range of long-term memory processes assessed in this study. It is concluded that at the doses employed, OXCZ has a slightly stimulant effect on some aspects of psychomotor functioning.

Adult↗

PubMed1993

Differential effects of lorazepam and oxazepam on priming.

The effects of lorazepam (2 mg), oxazepam (30 mg) and placebo on performance in implicit and explicit memory tasks were compared in a double-blind, independent group study with 36 healthy volunteers. Both benzodiazepines (BZs) impaired performance on the explicit task (free recall). However, only lorazepam impaired performance of the implicit task (word-stem completion). A similar pattern of drug effects was observed on a secondary task which used different instructions at stimulus presentation. BZ effects on the explicit task were more associated with levels of sedation (indexed by finger tapping speed) than their effects on the implicit task. It is concluded that both BZs impair episodic memory but only lorazepam impairs priming.

Adolescent↗

PubMed1991

The effects of repeated doses of clomipramine and alprazolam on physiological, psychomotor and cognitive functions in normal subjects.

The effects of a 10 day administration of clomipramine (25-50 mg t.i.d.), alprazolam (0.25-0.75 mg t.i.d.) and placebo were assessed in normal volunteers in a double-blind cross-over study. A battery of physiological, psychomotor and cognitive tests was administered both before and 3 h after drug on days 1, 5 and 10. The effects of alprazolam on EEG and evoked potentials were characteristic of benzodiazepines; clomipramine had little effect. In contrast, reaction speed was markedly slowed by clomipramine but little affected by alprazolam. Neither drug produced any accumulation of effect on a verbal recall task but neither did tolerance develop to the acute impairments produced by active treatments. Alprazolam produced an increase in levels of forgetting, especially on day 5. Subjective ratings for mood and bodily symptoms were adversely affected by clomipramine but little altered by alprazolam. It is suggested that some of the differences between drug treatments may be due to differences in the speed of onset of tolerance.

Adult↗

PubMed1991

Does tolerance develop to the sedative and amnesic effects of antidepressants? A comparison of amitriptyline, trazodone and placebo.

The psychomotor, sedative and memory effects of a sedative, anticholinergic antidepressant (amitriptyline), a sedative antidepressant (trazodone) and placebo were compared in a double-blind, cross-over study with 12 healthy volunteers. Amitriptyline (37.5 mg) and trazodone (100 mg) were administered for the first 7 days of treatment and in double-dosage for the next 7 days of treatment. Subjects completed a battery of tests before and 2 h after drug administration on days 1, 8 and 14. Over the 2 weeks of treatment, there was no accumulation of effects but subjects experienced marked sedation and psychomotor impairments following a daily dose of both active drugs. Although both amitriptyline and trazodone produced impairments on memory tasks, the effect of amitriptyline was significantly greater and may reflect its anticholinergic action over and above global sedative effects. Tolerance to the effects of amitriptyline built up differentially over measures of sedation, psychomotor function and memory.

Adult↗

PubMed1991

Models of memory dysfunction? A comparison of the effects of scopolamine and lorazepam on memory, psychomotor performance and mood.

The effects on memory, psychomotor functions and mood of intramuscular scopolamine (0.3 mg, 0.6 mg) were compared with those of oral lorazepam (2 mg) and placebo. Thirty-six volunteers took part in a double-blind, independent groups design. Subjects completed a battery of tests 1 and 3 h after drug administration. Both doses of scopolamine produced levels of sedation comparable to that produced by lorazepam. The time course of effects of scopolamine and lorazepam differed but the pattern of psychomotor impairments and amnestic effects produced was very similar. In terms of mood, lorazepam had an anxiolytic effect whereas scopolamine increased ratings of anxiety. Levels of sedation, indexed by either subjective ratings or motor retardation (tapping speed), were related more to psychomotor performance than to performance on memory tasks. The results suggest that benzodiazepines and scopolamine have similar amnestic and sedative effects and as such may not offer distinct models of memory dysfunction.

Adult↗

PubMed1991

Differentiating the sedative, psychomotor and amnesic effects of benzodiazepines: a study with midazolam and the benzodiazepine antagonist, flumazenil.

Sixteen healthy volunteers were administered midazolam followed by placebo or the benzodiazepine antagonist, flumazenil, in a double-blind, cross-over study. Flumazenil reversed midazolam-induced sedation on the subjective, psychophysiological and motor indices used. In contrast, there was little evidence of any reversal of amnesic effects, which were assessed using both direct (explicit) and indirect (implicit) measures of memory. Results are discussed in terms of dissociating the sedative and amnesic effects of benzodiazepines.

Adult↗