bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that imipramine‐induced postural hypotension may be centrally mediated
Authors: Middleton H. C. , Nutt D. J. , Anastassiades P. 
Published: December 2004

AbstractThe acute effects of imipramine upon cardiovascular reflexes have been studied in normal volunteers. Respiratory sinus arryhthmia, blood pressure and heart rate responses to standing, heart rate response to Valsalva's manoeuvre and the heart rate and blood pressure responses to isometric exercise were measured before and after 100 mg and 40 mg imipramine orally on separate occasions. Neither dose had an appreciable effect upon respiratory sinus arrhythmia (RSA), heart rate response to Valsalva or the responses to isometric exercise.Imipramine caused dose‐related rises in resting heart rate and blood pressure. In view of the unchanged RSA these cannot be attributed to vagal blockade and may reflect peripheral noradrenaline reuptake inhibition. Imipramine profoundly altered the heart rate response to standing in a dose‐related manner. This suggests an impairment of the orthostatic reflex. The presence of normal responses to the Valsalva manoeuvre and isometric exercise suggests that peripheral mechanisms were intact, and it is therefore likely that impairment of the orthostatic reflex is due to the effect of imipramine upon central monoaminergic neurones normally involved in this response.
The pharmacodynamic influence of three benzodiazepines on rapid eye movements, K‐complexes and sleep spindles in healthy volunteers
Authors: Kubicki St. , Haag‐Wüsthof C. , Röhmel J. , Herrmann W. M. , Scheuler W. 
Published: December 2004

Abstract‘Equipotent’ doses of lormetazepam, triazolam and flunitrazepam were studied for their effect on K‐complexes, sleep spindles and rapid eye movements (REM). Receptor affinity was used as the criterion for equipotency. This showed that triazolam, lormetazepam and flunitrazepam display a ratio to each other of 1:2:4. However, it was found that lormetazepam caused only slight changes in the three neurophysiological parameters despite being given at twice the dose considered to be equipotent. In contrast, triazolam and flunitrazepam produced a great reduction in the number of K‐complexes, a marked increase in sleep spindles and a substantial reduction of REM activity; both substances suppressed the first REM period, and flunitrazepam even suppressed the second in some cases. The influence of all three benzodiazepines on the dissociation of K‐complexes and sleep spindles is, however, equal; epochs with either K‐complexes or sleep spindles are favoured compared to epochs with both K‐complexes and sleep spindles. The general reduction in the number of K‐complexes and increase in sleep spindles can be interpreted as a sleep‐protective effect. However, the parameter for dose‐finding should be REM suppression, since this has the most profound adverse effect on the cyclical structure of sleep—now considered to be the most reliable indicator of a balanced sleep pattern.
A double‐blind dose‐finding study of rolipram in patients with major depressive disorder
Authors: Bennie E. H. , Chakravarti S. K. , Jarman C. M. B. , Khan K. , Master D. , Murray G. H. , Meya U. , Soni S. D. , Shaw S. H. , White A. C. 
Published: December 2004

AbstractRolipram improves signal transmission in central noradrenergic neurones with a novel mechanism of action: enhanced noradrenaline (first messenger) synthesis and release, and inhibition of cAMP (second messenger) breakdown. Several comparative trials to prove antidepressant activity are under way. Results of a multicentre double‐blind trial with three different dosages of rolipram involving 98 patients will be presented. Reponse rates in all dosages were similar and comparable to those reported in the literature on tricyclic antidepressants. In addition rolipram was tolerated well. A significant relationship between dosages and effects, however, could not be established.
A serotonin hypothesis of panic disorder
Authors: Kahn Rene S. , Van Praag Herman M. 
Published: December 2004

AbstractDespite numerous animal studies indicating an important role of serotonin (5‐HT) in anxiety, 5‐HT's function in the regulation of human anxiety has hardly been studied. Recent clinical studies suggest an involvement of 5‐HT systems in panic disorder. This paper will briefly review the pertinent data on 5‐HT and panic disorder and propose a specific hypothesis on 5‐HT abnormalities in that disorder.
Chronic diazepam treatment: Effect of dose on development of tolerance and incidence of withdrawal in an animal test of anxiety
Authors: Sandra E. 
Published: December 2004

AbstractThe effect of the treatment dose of diazepam was assessed on the rate of development of tolerance to diazepam's effects on rat behaviour in the elevated plus‐maze test of anxiety. Tolerance developed more rapidly when treatment was with the higher dose: after 14 days when rats were given 2·5 mg/kg/day, but not until 21 days when they were given 1 mg/kg/day. When rats were tested undrugged 36 h after the last of 14 daily doses of diazepam (2·5 mg/kg) they showed behavioural changes indicating increased anxiety. Rats tested at this time with a lower dose of diazepam (1 mg/kg) also showed changes indicating increased anxiety compared with the control scores. This indicates that a more gradual tapering of doses would be necessary to avoid withdrawal responses.
Comparison of the effects of fengabine, a novel antidepressant, with those of amitriptyline on psychomotor and autonomic functions in healthy volunteers
Authors: Theofilopoulos N. , Gray C. M. , Szabadi E. , Bradshaw C. M. 
Published: December 2004

AbstractTwo single doses (300 and 600 mg) of fengabine, a novel antidepressant, a single dose (50 mg) of amitriptyline, and a single dose of placebo were taken by sixteen male healthy volunteers (18–30 years), in weekly experimental sessions, according to a balanced double‐blind cross‐over design. In Part A (eight subjects) subjective mood state, psychomotor performance and some baseline autonomic functions were measured before, and 1, 3 and 5 hours after drug taking. In Part B, cholinoceptor‐mediated tissue responses (pilocarpine‐evoked miosis and carbachol‐evoked sweating) were measured two and a half hours after drug taking. Fengabine and placebo did not affect any of the test results, whereas amitriptyline had effects consistent with the sedative (reduction in alertness, impairment of psychomotor performance) and antimuscarinic (reduction in salivation and carbachol‐evoked sweating) properties of the drug.
The effects of lormetazepam on contractile force of the gastrocnemius muscle and on memory of healthy young volunteers
Authors: Deijen J. B. , Heemstra M. L. , Orlebeke J. F. , De Vries J. , Neijzen J. B. M. 
Published: December 2004

AbstractOne group of 10 young subjects were tested twice; in one test session 2 mg lormetazepam, in the other session placebo was administered, in random order. One subject dropped out. In one test session contractile force measurements were made six times; one measurement took place before treatment and the other measurements after treatment with the study medication. Each measurement of contractile force consisted of pushing weights of 0 to 10 kg and exerting maximal force. The corresponding electromyogram (EMG) of the gastrocnemius muscle was recorded. For the forces of 0 to 10 kg the regression was established of EMG on contractile force. Treatment effects on memory were investigated by means of a selection of tests, covering short‐term and long‐term memory, in terms of recall and recognition. Analyses of covariance were performed on the regression coefficients of EMG/ contractile force and on the data of maximally exerted force, the pre‐treatment scores serving as covariate. These analyses did not result in any difference for the two treatment conditions, leading to the conclusion that the administration of lormetazepam did not have any direct action on the contractile systems of human muscle. The t‐tests performed on the memory data resulted in a significant impairment of performance on the long‐term memory tasks, whereas short‐term memory was not impaired. It is concluded that, in accordance with previous research, the administration of lormetazepam results in an impairment in the acquisition of new information in long‐term memory, but also in impaired retention.
Cannabis and human social behaviour
Authors: Marks David F. , Pow Gillian M. 
Published: December 2004

AbstractAlthough an illicit substance, cannabis is a commonly used recreational drug. In spite of its social usage, relatively little scientific research has been directed towards the question of its social effects and motivations for use. In this experiment five doses of cannabis up to a maximum of 14 mg Δ‐9‐THC were administered double‐blind and in a balanced order. Self‐ratings of ‘highness’, intoxication, and social effects were obtained and also subjects' ratings of each other's behaviour. Similar ratings were obtained from six independent judges who viewed videotapes. Significant non‐linear dose‐response effects and interactions with acquaintanceship provide further evidence of the importance of setting in determining cannabis effects.
Sleep inertia following triazolam‐induced recovery sleep
Authors: Balkin T. J. , O'donnell V. M. , Kamimori G. H. , Redmond D. P. , Belenky G. 
Published: December 2004

AbstractThe effect of triazolam on prior‐sleep‐mediated performance deficits (sleep inertia) was assessed. On Day 1, subjects (45 healthy males, aged 18–39, tested in groups of two to four) reported to the laboratory at 0800 h, at which time electrodes were attached for continuous ambulatory recordings of EEG, EMG, EOG, and EKG. Addition tests of 3 min duration were administered at 1400, 1405, 1410, 1415, 1420, and 1425 h. After each test a Stanford Sleepiness Scale (SSS) was given to assess self‐rated sleepiness. Subjects were then kept awake until 0800 h on Day 2, when they were administered 0·5, 0·25, 0·125 mg triazolam or placebo. Subjects attempted to sleep from 0800 to 1400, at which time they were awakened (if asleep) and again administered the addition tests and SSSs. of 45 subjects, 24 were asleep during the 5 min period prior to testing, and only these were included in the analyses. A main effect of Day indicated decrements in addition speed on Day 2, F(1,20)=10·54, p=0·004, and a Day × Test interaction indicated sleep inertia effects, F(5,100)=6·18, p=0·0001. Differential drug effects were indicated by a significant Day × Drug interaction, F(3,20)=3·19, p=0·046, and post‐hoc analyses revealed that the number of problems attempted was significantly lower on Day 2 only for the 0·5 mg triazolam group. It was concluded that sleep inertia is exacerbated by 0·5 mg triazolam.
Metabolism of the benzodiazepine antagonist 11C‐Ro 15‐1788 after intravenous administration in man
Authors: Swahn Carl‐Gunnar , Persson Anders , Pauli Stefan 
Published: December 2004

AbstractThe metabolic fate of the benzodiazepine antagonist RO 15‐1788 labelled with 11C was studied in plasma from human subjects after intravenous administration in connection with positron emission tomography. Ro 15–1788 and its metabolites were separated by thin‐layer chromatography and the radioactivity in the different compounds was determined. 11C‐Ro 15–1788 was extensively and rapidly metabolised to the corresponding free acid. At 36 minutes after administration only 50% of the radioactivity in plasma represented unchanged compound.
A case of Parkinson's disease exacerbated by fluoxetine
Authors: Chouinard Guy , Sultan Sarah 
Published: December 2004

AbstractFluoxetine (Prozac®) is a potent serotonin (5‐HT) reuptake inhibitor which has rapidly gained popularity as a first‐line antidepressant due to its favourable side‐effect profile. However, it has recently been reported to worsen drug‐induced parkinsonism when used in conjunction with neuroleptics (Bouchard et al., 1989; Tate, 1989; Brod, 1989). Since fluoxetine inhibits hepatic microsomal enzymes, a pharmacokinetic interaction cannot be ruled out in such cases — the drug is known to interact with other psychotropic drugs such as MAO inhibitors (Sternbach, 1988; Feighner et al., 1990) and tricyclic antidepressants (Bell and Cole, 1988; Vaughan, 1988; Goodnick, 1989; Schraml et al., 1989; Kahn, 1990) via this mechanism among others. So far, fluoxetine has not been reported to worsen symptoms in patients with Parkinson's disease (PD) who have never received neuroleptics. Bouchard et al. (1989) observed that other selective 5‐HT reuptake inhibitors might exacerbate PD, and Meltzer et al. (1979) described a bipolar patient who developed an acute dystonic reaction, with parkinsonian rigidity and increased serum prolactin when treated with fluoxetine for psychotic depression. Fluoxetine has been implicated in the development of neuroleptic malignant syndrome (Halman and Goldbloom, 1990) and akathisia (Lipinski et al., 1989; Baldwin et al., 1991), which may also be linked to central dopaminergic blockade. A recent review of extrapyramidal tract disorders in association with fluoxetine and fluvoxamine, another selective 5‐HT uptake blocker, noted the absence of unambiguous cases and the lack of objective documentation of psychopathological and neurological changes, even though evidence for a causal relationship was compelling (Baldwin et al., 1991).
Benzodiazepines, amnesia and sedation: Theoretical and clinical issues and controversies
Authors: King D. J. 
Published: December 2004

AbstractThe amnestic effect of benzodiazepines, first described in 1965, and the subsequent attempts to identify the precise nature of this effect, are reviewed. The difficulty in deciding to what extent this effect is secondary to the sedative action of these drugs is shown by the lack of agreement between studies. Nevertheless, it is concluded that, given the right experimental design, all benzodiazepines can be shown to cause an anterograde amnesia which is probably primarily a result of reduced attention or rehearsal and secondary to sedation. Its onset, degree and duration are influenced by dose, rate of absorption, route of administration, potency and the receptor occupancy rate of the particular benzodiazepine involved, but plasma elimination t½ appears to be relatively unimportant. The clinical relevance of this for the long‐term use of hypnotics and anxiolytics is not clear. Tolerance appears to be greater than for the anxiolytic but less than the sedative or anticonvulsant effect of benzodiazepines. It seems that transient amnestic effects could occur in chronic users related to post‐dose, peak benzodiazepine levels. The great variability in individual response means that transient amnesia is a potential adverse drug reaction in certain individuals taking benzodiazepines.
The plasma haloperidol and reduced haloperidol concentrations in chinese schizophrenic patients: Relationship between reduced haloperidol/haloperidol ratio and red blood cell haloperidol reductase activity
Authors: Wong B. Y. M. , Chan Mo‐Yin , Wong M. T. H. , Lieh‐Mak F. 
Published: December 2004

AbstractFifteen chinese schizophrenic patients were given titrated doses of haloperidol (0.05‐0.42 mg/kg) for two weeks. All these 15 patients were in clinical remission on maintenance dose of haloperidol. The mean plasma haloperidol and reduced haloperidol concentrations were 16.8 ± 4.8 ng/ml and 13.6‐ 5.7 ng/ml respectively. The plasma RHAL/HAL ratio was in the range of 0.13±1.94. These values were similar to that reported for the Japanese population. The frequency distribution appeared to be bimodal. RBC reductase activity were found to be distributed normally and no correlation was found between plasma RHAL/HAL ratio and RBC reductase activity.
Possible relationships between carbamazepine metabolites levels and prophylactic efficacy
Authors: Kudriakova Tatyana B. , Sirota Lev A. , Kostyukova Elen G. , Gorkov Vladimir A. 
Published: December 2004

AbstractLevels of carbamazepine, carbamazepine‐10,11‐epoxide and −10,11‐diol were measured in the plasma of 40 patients with affective disorders chronically treated with carbamazepine. Steady‐state plasma levels of carbamazepine were not related to the degree of prophylactic response. In contrast, the mean plasma concentrations of the −10,11‐epoxide metabolite of carbamazepine were significantly lower in patients with complete response than in patients with partial response or in nonresponders. The ratios of carbamazepine‐10,11‐diol concentrations to the parent drug dose were found to be significantly different in the three response groups. These results suggest that the pharmacokinetic parameters of the metabolites might be used for the prediction of individual prophylactic efficacy at the initial stage of carbamazepine therapy.
Physical dependence following zopiclone usage: A case report
Authors: Thakore J. , Dinan T. G. 
Published: December 2004

AbstractA single case report is presented in which zopiclone was used in a patient as a hypnotic. The patient developed physical dependence. It is suggested that the adverse effects of zopiclone relate to its mechanism of action. Like other hypnotics it binds to the gamma‐aminobutyric acid (GABA)‐benzodiazepine‐chloride ionophore receptor complex. This may explain the means by which zopiclone can cause dependence.
A comparison of the effect of lofepramine, maprotiline and placebo on information processing in healthy volunteers
Authors: Hopes H. , Wandmacher J. 
Published: December 2004

AbstractSingle oral doses of lofepramine (140 mg), maprotiline (100 mg), and placebo were administered in a randomized three‐way crossover design with 1 week wash‐out between administrations to 12 healthy male volunteers. Before, and 1, and 3 h post‐administration a battery of performance tests was administered which included a digit‐matching paradigm and a reaction test separating recognition and motor time. In contrast to maprotiline, lofepramine did not impair speed and accuracy of cognitive performance.
The life expectancy of schizophrenic patients with tardive dyskinesia
Authors: Inada Toshiya , Koshiishi Mika , Ohnishi Kimio , Yagi Gohei 
Published: December 2004

AbstractRelationships between tardive dyskinesia (TD) and the life expectancy of schizophrenic patients who suffer it were examined in two studies over a 50‐month period. In a prospective study, the mortality rate was found to be higher in patients with TD than in those without. This suggests either that TD is a factor tending to precipitate death, or else that it is an indication that the final period of life has been reached. The failure in the prospective study to detect medical factors which would discriminate between those TD patients who died and those who remained alive, as well as the finding of a significantly older age at death of patients with TD in the retrospective study may both support this idea. No significant differences were observed in the retrospective study in the prevalence of TD between 35 pairs of age‐matched deceased and living patients. The effects of TD on life expectancy are subtle; the present results are consistent with the possibilities both that TD reduces life expectancy and that it appears at the end‐stage of life.
The effects of acute and repeated doses of moclobemide on psychomotor performance and cognitive function in healthy elderly volunteers
Authors: Kerr J. S. , Fairweather D. B. , Hindmarch I. 
Published: December 2004

AbstractThe effects of moclobemide, a new selective and reversible MAO‐A inhibitor, on cognitive function and psychomotor performance were measured in 12 healthy elderly male volunteers (with a mean age of 72.5 years). Subjects received moclobemide 200 mg, amitriptyline (positive internal control) 25 mg or placebo twice daily and were assessed on a battery of psychometric tests on the mornings following the first (acute) day and seventh (sub‐chronic) day. The tests were: Choice Reaction Time; Tracking; Critical Flicker Fusion Threshold; Memory Scanning; Continuous Attention Task; the Leeds Sleep Evaluation Questionnaire and a Visual Line Analogue Rating Scale. The results show that amitriptyline produced impairment of cognitive and psychomotor functions. Moclobemide, however, did not disrupt sleep or cause daytime sedation, and remained neutral in the assessment of behavioural toxicity.
A comparative study of on‐the‐road and simulated driving performance after nocturnal treatment with lormetazepam 1 mg and oxazepam 50 mg
Authors: Volkerts E. R. , van Laar M. W. , van Willigenburg A. P. P. , Plomp T. A. , Maes R. A. A. 
Published: December 2004

AbstractThe main purpose of this study was to compare the sensitivity of a driving simulator test model (TS2) with a standard on‐the‐road driving test, after one night treatment with lormetazepam 1 mg, oxazepam 50 mg (as a verum) and placebo. The secondary purpose was to measure the effects of the intended drugs and placebo in the same subject sample, after two treatment nights in the morning and in the afternoon, on on‐the‐road driving performance. Eighteen healthy male volunteers received the three treatments (2 consecutive nights each) according to a double‐blind, three‐way crossover design. Time of administration was set at 22.00 hours each night. An on‐the‐road driving test and a simulator driving test were conducted in the morning following the first night. After the second treatment night, on‐the‐road driving tests were performed in the morning and in the afternoon. The on‐the‐road driving test consisted of operating an instrumental automobile over a 100 km highway circuit at a constant speed (90 km/h) and constant steady lateral position between the right lane boundaries. Primary performance measure was the SD of lateral position (SDLP). The simulator test consisted of repeatedly performing ‘curve‐following’ manoeuvres, which was the main tracking control task, while simultaneously reacting to secondary visual signs. Test parameters were the number of correctly executed manoeuvres (TC) and reaction time (RT). Oxazepam 50 mg seriously impaired, and lormetazepam 1 mg slightly impaired, on‐the‐road driving performance in the morning, both after the first and second treatment night. The drugs produced no significant effects in the afternoon test following the second night. In contrast with these results, neither oxazepam 50 mg nor lormetazepam 1 mg affected simulator tracking control after one night. No deterioration was found for reaction time. Correlational and multiple regression analyses were applied to determine relationships between SDLP, TC and RT. The major conclusion of this study was that the TS2 driving simulator test does not predict residual drug effects in the on‐the‐road driving test, and seems to be a less sensitive measure of sedative drug‐induced impairment in contrast to the on‐the‐road driving test.
Studies on the binding of [3H]flumazenil and [3H]sarmazenil in post‐mortem human brain
Authors: Hall H. , Litton J.‐E. , Halldin C. , Kopp J. , Sedvall G. 
Published: December 2004

AbstractTwo benzodiazepine analogues, [3H]flumazenil and [3H]sarmazenil, were used to study the GABAA/benzodiazepine receptor complex in human post‐mortem brain using in vitro receptor assays on homogenates and whole hemisphere autoradiography. Both radioligands bound in a saturable manner to single binding sites in the tissue preparations from any brain region. The highest levels of binding were found in the cortical regions and in cortex cerebelli. Both [3H]flumazenil and [3H]sarmazenil were excellent radioligands for autoradiography with high binding in cerebral and cerebellar cortex with no or very low binding in areas with white matter. The addition of a high concentration of flumazenil or clonazepam did not inhibit the binding of [3H]sarmazenil to granule cells in the cerebellum while the binding of [3H]flumazenil was abolished completely in all regions. The results show that with the two different radioligands, one an antagonist and one a partial inverse agonist, the binding pattern to GABAA/benzodiazepine receptor complex is approximately similar in most brain regions. The additional binding seen in the cerebellum with [3H]sarmazenil is suggested to be due to binding to an α6‐containing complex.