Effects of fluoxetine on psychomotor performance, cognitive function and sleep in depressed patients.
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Aged↗
Biomedical subjects
J S Kerr
Publications and source records attributed to J S Kerr.
A placebo controlled double-blind evaluation of the pharmacodynamics of fengabine vs amitriptyline following single and multiple doses in elderly volunteers.
1. The effects of fengabine were compared with those of amitriptyline in healthy elderly volunteers. Doses were administered double-blind and assessments were made before and after ingestion. 2. Psychomotor performance and cognitive ability were measured using tests of choice reaction time, tracking, critical flicker fusion threshold, memory scanning and word recognition. Subjective feelings were assessed using the Leeds sleep evaluation questionnaire (LSEQ) and line analogue rating scales (LARS). 3. Pharmacokinetic data suggest that fengabine may induce its own metabolism following repeated dosing. 4. The findings of this study show that fengabine 200 mg and 400 mg does not produce any noticeable behavioural toxicity in elderly volunteers, in contrast to amitriptyline which had a disruptive effect throughout.
Administration, Oral↗
Synthesis, chemical, and biological properties of vinylogous hydroxamic acids: dual inhibitors of 5-lipoxygenase and IL-1 biosynthesis.
Vinylogous hydroxamic acids (3-(N-hydroxy-N-alkylamino)-2-propen-1-ones, VHA) were prepared as antiinflammatory agents. The synthesis, chemical properties, and in vitro biological activities of these relatively unexplored compounds are described. The VHAs were prepared by condensation of the appropriate N-substituted hydroxylamine with any of the three reagents: a 1,3-dicarbonyl compound (method A); a vinylogous amide (method B); or an alkynone (method C). The VHAs exist as one or more tautomers in solution with the relative proportions of each being dependent upon the structure of the VHA, solvent, and pH. VHAs undergo some of the typical reactions of hydroxamic acids as well as those of vinylogous amides. VHAs are active as inhibitors of 5-lipoxygenase and of IL-1 biosynthesis in vitro, which do not inhibit other enzymes of the arachidonic acid cascade. They have been shown by ESR studies to bring about inhibition of soybean type 1 15-lipoxygenase by reduction of the active site iron.
Animals↗
Correlation between doses of oxazepam and their effects on performance of a standardised test battery.
Ten different doses of oxazepam (ranging from 7.5 to 50 mg) or placebo were administered to a total of 28 female subjects in three separate studies. Subjects completed a battery of psychometric tests at 1 and 2 h postdose. The tests included critical flicker fusion, choice reaction time and a tracking task. Following separate analyses of variance, effect sizes (Cohen's d) were calculated for each dose at each dependent variable. These effect sizes were then correlated with the dose of drug administered, using regression analyses. It was found that the doses correlated highly with most of the psychometric variables determined, implying that the test battery is sensitive to drug effects.
Adult↗
Psychomotor performance in smokers following single and repeated doses of nicotine gum.
The psychomotor effects of single and repeated doses of 2 mg nicotine gum were investigated in 13 regular smokers who had abstained from tobacco overnight. In comparison to baseline, a first dose of nicotine led to significantly raised critical flicker fusion thresholds, faster motor reaction times, improved compensatory tracking performance, and faster short-term memory reaction times. Performance after a second and third dose of nicotine remained significantly improved on all measures in comparison to baseline, and absolutely improved when comparing first and third nicotine doses on measures of sensorimotor performance. Throughout, comparisons with a placebo gum condition confirmed that these effects were genuine and not subject to the development of acute nicotine tolerance, suggesting that the enhancement of psychomotor performance experienced by smokers after a first cigarette may be maintained by repeated smoking.
Administration, Oral↗
The effects of acute and repeated doses of zolpidem on subjective sleep, psychomotor performance and cognitive function in elderly volunteers.
We gave 24 healthy elderly volunteers with a perceived sleep onset of at least 30 minutes zolpidem 5 mg, zolpidem 10 mg, or placebo for 7 days in a double-blind, three-way, crossover study. The morning after nocturnal dosing, psychomotor performance and cognitive ability were measured using tests which are sensitive to the residual effects of hypnotics and to the effects of drugs on various indicators of sleep quality. The tests were: Choice Reaction Time; Tracking; Critical Flicker Fusion Threshold; Memory Scanning; Word Recognition; the Leeds Sleep Evaluation Questionnaire and Line Analogue Rating Scales. Zolpidem produced a subjective improvement in sleep but did not impair performance the following day. Furthermore, during repeated administration, there was no tolerance to the effects of sleep latency and quality of sleep, nor adverse effects on task performance.
Aged↗
The effects of acute and repeated doses of suriclone on subjective sleep, psychomotor performance and cognitive function in young and elderly volunteers.
Suriclone is a new anxiolytic drug belonging to the family of cyclopyrrolones. The effects of acute and repeated doses of suriclone on subjective sleep, psychomotor performance and cognitive function were compared to those of placebo in young and elderly volunteers. Young volunteers randomly received suriclone 0.2 mg, 0.3 mg, 0.4 mg or placebo tid, and the elderly received suriclone 0.1 mg, 0.2 mg or placebo tid. After the first single dose and after a three-day treatment, subjects completed at 1, 2, 4, 12 and 24 h after drug administration the following battery of psychomotor and cognitive tests: critical flicker fusion threshold, choice reaction time, simulated car tracking test, the stroop test and the Sternberg memory scanning task. Visual analogue scales and the Leeds sleep evaluation questionnaire were also administered during the study. No significant effects of suriclone compared to placebo were seen on the psychomotor tests both in young and elderly volunteers. The only significant result was an improvement of the ease of getting to sleep in the young with 0.4 mg suriclone tid. In conclusion, there is little evidence to suggest that suriclone produces any measurable behavioural toxicity, so often seen with many of the benzodiazepines, in either young or elderly subjects.
Adult↗
Nutritional aspects of collagen metabolism.
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Amino Acids↗
Shape changes due to functional appliances.
Functional appliances are now routinely used in orthodontic treatment to correct anteroposterior skeletal discrepancies, based on the assumption that existing functional patterns can be modified to yield a new morphological pattern. However, the mechanisms by which this correction occurs remain in dispute as current measurement procedures, primarily mathematical, do not adequately describe shape changes. This paper introduces a new measurement method, Fourier descriptors, to clinical dentistry.
Adolescent↗
An evaluation of 2-benzyl-1-naphthol (DuP 654) analogs as systemic anti-inflammatory agents.
DuP 654 (2-benzyl-1-naphthol) is a topically active anti-inflammatory agent that was evaluated in phase II clinical trials as an anti-psoriatic agent. The compound is a potent 5-lipoxygenase inhibitor and exhibits inhibitory activity against lipopolysaccharide-stimulated release of interleukin-1 from human monocytes. DuP 654 cannot be used as a systemic anti-inflammatory compound due to its rapid and extensive metabolism. Fifteen analogs were synthesized in an attempt to block the systemic route(s) of metabolism. The compounds were evaluated (IP and PO) in the rat carrageenan paw edema inflammation model with plasma samples taken at 1, 2, 3, and 4 hours post-dose. Substitutions at the 4- and/or 8-positions on the naphthol, and/or on the benzyl group of the DuP 654 molecule were unsuccessful in achieving an analog which displayed both oral activity in the inflammatory model and high plasma levels without manifesting toxicity. The low plasma levels of some analogs may indicate poor absorption, high volume of distribution, or that the substitution did not inhibit the high hepatic "first-pass" metabolism observed with DuP 654. Other compounds not studied but similar in structure to DuP 654 may exhibit rapid and extensive metabolism.
Administration, Topical↗
The effects of paroxetine, alone and in combination with alcohol on psychomotor performance and cognitive function in the elderly.
Fifteen healthy male volunteers aged over 60 years received acute and repeated doses of paroxetine 20 mg or placebo, and acute doses of lorazepam 1 mg (as a positive internal control) with or without alcohol (0.6 g/kg of body weight) administered openly in a double blind balanced crossover study in which each subject acted as his own control. Psychomotor performance and cognitive function were assessed using a test battery which included critical flicker fusion, choice reaction time, compensatory tracking, Stroop and memory scanning tests. Subjective ratings of mood and sleep were recorded using line analogue rating scales. The pattern of results indicated that paroxetine had little or no effect on most of the test variables, and in some instances (critical flicker fusion thresholds) improved information processing ability. This was in marked contrast to the lorazepam verum which produced sedation and disruption of performance. Paroxetine had a slight antagonistic effect on alcohol induced sedation whereas impairment of performance with lorazepam was potentiated by co-administration of alcohol. The low behavioural toxicity of paroxetine in elderly volunteers has important implications for the pharmacotherapy of depression.
Aged↗
Phospholipase A2 (PLA2) activity in bovine pulmonary artery endothelial cells.
We have investigated the role of recombinant human interleukin-1 beta (rIL-1 beta) and recombinant human tumor necrosis factor alpha (rTNF-alpha) on PLA2 activity, protein synthesis and eicosanoid production in bovine pulmonary artery endothelial cells. Cellular PLA2 activity increased 4-fold and production of PGE2 increased 3-fold at 1-2 hrs in the presence of 10 units/ml rIL-1 beta. PLA2 activity increased 3-fold at 30 min and PGE2 production increased 2-fold with 5 x 10(-9) M rTNF-alpha. The data show that endothelial cells respond more rapidly to rIL-1 beta (2-6 hr) and rTNF-alpha (30 min) than do chondrocytes and synovial cells (6-16 hrs), suggesting endothelial cells may play a primary role in initiating the inflammatory response.
Animals↗
Separate and combined effects of the social drugs on psychomotor performance.
Ten female subjects (five smokers and five non-smokers) performed a choice reaction time task (CRT), a compensatory tracking task (CTT), a short-term memory task (STM) and were tested for their critical flicker fusion threshold (CFF) at set points over 4 h after the administration of each possible combination of nicotine (2 mg gum or placebo), caffeine (250 mg capsule or placebo) and alcohol (30 g or placebo). Memory and motor function were shown to be facilitated by nicotine or caffeine, and the debilitating effects of alcohol were frequently antagonised by either drug. In spite of the differences in their neuropharmacological actions, combinations of nicotine, caffeine and alcohol may be compared through their effects on common information processing mechanisms involved in psychomotor performance.
Adult↗
Alcohol, cognitive function and psychomotor performance.
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Caffeine↗
The effects of alcohol and other drugs on psychomotor performance and cognitive function.
The effects of four doses of alcohol (0.25 g/kg-1 g/kg) and placebo on a standard test battery of cognitive and psychomotor performance are described. The tests included critical flicker fusion threshold, choice reaction time, tracking and memory scanning. The results of this experiment are compared with those of a number of similar studies which examined the effects of other psychoactive substances. Using relative effect sizes, the behavioural toxicity of alcohol is compared with the effects of these other drugs on psychomotor performance and cognitive function.
Adult↗
Kinetics of phospholipase A2, arachidonic acid, and eicosanoid appearance in mouse zymosan peritonitis.
Intraperitoneal injection of zymosan into mice induces a peritonitis characterized by cellular influx, plasma leakage and the appearance of arachidonic acid (AA) metabolites. We report that zymosan injection also stimulates the accumulation of AA, docosahexaenoic acid, linoleic acid, and phospholipase A2 (PLA2) activity. The amount of the unsaturated fatty acids (UnFA) varies both with the zymosan dose and time. Significantly increased levels of UnFA were first detected 15 min after zymosan injection. Maximal levels of the UnFA were reached 1 to 2 h post zymosan injection (AA: 725 +/- 29 ng/mouse, docosahexaenoic acid: 296 +/- 23 ng/mouse, linoleic acid: 4489 +/- 179 ng/mouse) and declined to saline control levels by 8 h. PLA2 activity was significantly increased 5 to 15 min after zymosan injection. Maximal levels of PLA2 activity occurred 15 to 30 min after zymosan injection (31.8 +/- 9.1 nmol phospholipid/mg protein/h) and then decreased by 30% through 24 h. Neither the appearance of UnFA nor PLA2 activity correlated with cellular influx, but both were coincident with plasma exudation at 5 to 15 min after zymosan. However, maximal exudation occurred 1 to 2 h post zymosan injection similar to that seen with the UnFA but not PLA2. These latter results suggest that a significant portion of the UnFA found in the peritoneal cavity of zymosan-injected mice originates from the plasma. PLA2 activity at the early time points (5 to 15 min) may also contribute to the levels of UnFA via hydrolysis of tissue and/or cellular phospholipids.
Animals↗
Extracellular phospholipase A2 activity in two in vivo models of inflammation.
Two "in vivo" models of inflammation have been used to investigate the role of phospholipases A2 (PLA2) in inflammation. These models are casein-induced peritonitis in the rat and zymosan-induced peritonitis in the mouse. The extracellular PLA2 activities from peritoneal lavage fluid in these two models are similar: they are calcium dependent and have broad neutral pH optima. However, the relationship between extracellular PLA2 activity and cell influx in these models are not identical. In zymosan peritonitis, PLA2 activity preceded peak cell influx, reaching a maximum within 15 min after zymosan injection, while cell influx peaked by 8 hr. In casein-induced peritonitis, the PLA2 activity peaked at 24 hr, while cell influx continued through 48 hr. The origins of the PLA2 activities in both models remain unclear; one potential source is the plasma. Understanding the role of extracellular PLA2 activity in "in vivo" models, and investigating specific inhibitors in these models may aid in our understanding of the role of extracellular PLA2 in diseases such as rheumatoid arthritis, endotoxin shock and pancreatitis.
Animals↗
Characterization of extracellular phospholipase A2 (PLA2) activity in fluid and peritoneal cells from casein-treated rats.
Extracellular phospholipase A2 activity (PLA2) found in the fluid and cells of the peritoneal cavity of rats injected with casein is described. PLA2 activities from both the fluid and cells require Ca2+ and have pH optima of 7. Acid-extraction increased PLA2 activity in the polymorphonuclear leukocyte (PMN) homogenates 20-fold but not the PLA2 activity in the extracellular fluid. Acid extraction also increased the sensitivity of the PLA2 activities to standard inhibitors. Since the PLA2 activities described in this model have characteristics similar to other inflammatory PLA2s, including human synovial fluid PLA2, casein stimulation should prove useful for testing potential inhibitors.
Animals↗