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1.
Within a 4-h period after parturition, the ewe learns the odor of her lamb that will later allow recognition of her offspring
from an alien lamb. This study investigated the involvement of the cholinergic system in this olfactory learning. At parturition
and 2 h later, ewes received IM injections of saline (C group, n = 21), scopolamine methylbromide (METSCOP group, 100 μg/kg, n = 14) a peripherally acting muscarinic antagonist, a low dose of scopolamine hydrobromide (SCOP32 group, 32 μg/kg, n = 15) or a higher dose of scopolamine hydrobromide (SCOP100 group, 100 μg/kg, n = 18). Maternal behavior was observed at parturition and selective behavior was tested after 4 h of mother-young contact.
No differences in maternal behavior at parturition were found between groups. By contrast, the proportion of ewes showing
selectivity was significantly lower in the SCOP100 group (7/18) than in the METSCOP group (12/14, P = 0.01), SCOP32 group (12/15, P = 0.03), or C group (17/21, P = 0.01). In addition, saline-treated ewes, after having established their selective bond, received 100 μg/kg scopolamine and
were again tested for selectivity 20 min later. Only one out of the 17 tested ewes failed to recognize their lambs after this
treatment. These results indicate that intact central muscarinic transmission of the brain is required for the learning of
individual lamb odor at parturition but not for the recall of this information.
Received: 1 July 1996/Final version: 12 September 1996 相似文献
2.
The effects of intramuscular injections of diazepam (0.3 mg/kg) and scopolamine (8 g/kg) on memory processes and subjective moods were studied in 36 volunteers. Subjects (Ss) were tested in groups of four in a double blind procedure with treatments distributed according to a Latin square design. Lists of words were presented to Ss who were then tested with an immediate free recall test prior to drug administration. Following injection delayed free recall and recognition tests were given. Subsequently two sets of lists were presented separately and tested in the same fashion. Two of the lists in the last set were composed of words falling into distinct categories. Memory was additionally analyzed by testing immediate recall of digit sequences and employing a visual recognition test. Subjective moods were evaluated with a rating questionnaire.Both diazepam and scopolamine impaired memory functions although the action of the latter drug was more pronounced and prolonged. The deficit appeared to be in the storage process leaving retrieval processes unaffected. Scopolamine in addition interfered with organizational processes. Subjectively, scopolamine also produced a larger sedative effect than diazepam. 相似文献
3.
The effects of the muscarinic antagonists, scopolamine HBr and MeBr, a cholinesterase inhibitor, E2020, and K+ channel blockers, 4-aminopyridine (4-AP) and apamin, on the performance of rats in a delayed matching to position (DMTP)
task were examined. The percentage of correct choices (choice accuracy), number of trials completed and intertrial intervals
were measured. Discriminability and response bias were also calculated, using signal detection analysis. Scopolamine HBr (0.1 mg/kg),
but not scopolamine MeBr (0.1 mg/kg), significantly and consistently reduced the choice accuracy and discriminability, but
neither affected the other measurements. E2020 (0.03–1.0 mg/kg) had no effect on the baseline performance in the DMTP task,
but at 1.0 mg/kg, it significantly attenuated the deficits in choice accuracy induced by scopolamine. 4-AP (0.001–0.1 mg/kg)
had no effect on either baseline performance or deficits induced by scopolamine. Apamin (0.1–0.4 mg/kg) had no effect on choice
accuracy and discriminability. Apamin also failed to attenuate the scopolamine-induced deficits. When administered in combination
with scopolamine, apamin at 0.4 mg/kg significantly decreased the number of trials completed and increased the intertrial
interval relative to that of the control group. Taken together, these results demonstrate that K+ channel blockers (4-AP and apamin), unlike a cholinesterase inhibitor (E2020), fail to reverse the scopolamine-induced deficits
in the DMTP task.
Received: 27 March 1997/Final version: 19 June 1997 相似文献
4.
Drugs of abuse produce amnestic effects in humans and laboratory animals in a variety of tasks. Generally, only a few compounds
have been examined in any particular procedure. It was the goal of the present studies to examine drugs of abuse of different
pharmacological classes in rats responding under two behavioral schedules historically employed as experimental models of
memory: spatial alternation and matching to position. One group of rats responded under a single-response spatial-alternation
baseline with a 10-s delay and another group responded under a matching-to-position baseline with delay values of 3, 10 and
30 s. Performance under the spatial-alternation baseline was characterized by low variability and >90% accuracy. Under the
matching-to-position baseline, saline control percent accuracy was >95% at 3 s, >85% at 10 s and >70% at 30 s. Under spatial
alternation cocaine, d-amphetamine, pentobarbital, diazepam, phencyclidine, scopolamine and methscopolamine produced significant (P<0.05) effects on accuracy, whereas only cocaine, d-amphetamine, pentobarbital and phencyclidine disrupted accuracy under the matching-to-position baseline. These results suggest
that spatial alternation may be a more sensitive baseline for determining drug effects on working memory in the rat.
Received: 16 April 1997 / Final version: 25 November 1997 相似文献
5.
Scopolamine and lorazepam exert different patterns of effects in a test battery assessing stages of information processing 总被引:2,自引:0,他引:2
The effects of a single dose of scopolamine (0.5 mg) SC and of lorazepam (2.5 mg) PO were tested in two independent studies for their effects on performance in a psychometric battery which measured functions related to different stages of information processing. Attention and vigilance were measured by a continuous attention task and a vigilance task, respectively. Working memory and reasoning were evaluated by the rapid information processing and logical reasoning task; memory acquisition and storage were measured by pre- and post-drug immediate and delayed recall using visual material. The following pattern of effects was revealed: both scopolamine and lorazepam impaired performance in attentional and vigilance tasks as well as in the rapid information processing task significantly (P<0.05) when compared with their own placebo; in the logical reasoning task lorazepam significantly prolonged the time required to solve a problem; scopolamine did not have any effect on this task. Scopolamine impaired performance in the immediate recall but left delayed recall unaffected; lorazepam impaired only delayed recall, immediate recall remaining unaffected. These data suggest that scopolamine at this dose impaired mostly attention and early stages of information processes; lorazepam at the dose tested impaired also the later acquisition and encoding aspects of memory.This article is part of the Doctoral Thesis of B. Redemann 相似文献
6.
K. W. Lange T. W. Robbins C. D. Marsden M. James A. M. Owen G. M. Paul 《Psychopharmacology》1992,107(2-3):394-404
A group of ten patients with idiopathic Parkinson's disease (PD) was tested on a series of automated tests of learning, memory, planning and attention whilst either on or offl-dopa medication. Controlled with-drawal ofl-dopa interfered with aspects of performance on three of the tests that had previously been shown to be sensitive to frontal lobe dysfunction; a spatial working memory task, the Tower of London planning test, and a visual discrimination paradigm that also included intra- and extra-dimensional shift tests of selective attention. More specifically, errors were increased in the spatial working memory test, and both the accuracy and latency of thinking were impaired. Thinking time was significantly slowed followingl-dopa withdrawal, even though the possible contaminating effects on motor slowing were fully controlled by a yoked control procedure. Nine out of ten patients reached a further stage of the visual discrimination, set-shifting paradigm when on, rather than off,l-dopa medication. Spatial span was also impaired off medication, but there were no effects ofl-dopa withdrawal on tests of pattern and spatial recognition memory, simultaneous and delayed matching to sample or visuospatial conditional associative learning. Comparisons with a large control group confirmed previous findings that PD is associated with deficits on the majority of these tests. The results are discussed in terms of the fronto-striatal, dopamine dependent nature of some of the cognitive deficits found in PD, but the apparent dopamine-independent nature of deficits in other aspects of cognitive functioning, notably in tests of visual recognition memory and associative learning. 相似文献
7.
文拉法辛与舍曲林对抑郁症患者认知功能的影响比较 总被引:2,自引:0,他引:2
目的 探讨文拉法辛对抑郁症患者认知功能的影响.方法 将未用过抗抑郁药物和其他抗精神病药物的84例患者随机分为文拉法辛组(A组)和舍曲林组(B组),分别在治疗前和治疗12周后使用数字广度测验和空间工作记忆测验评定工作记忆改善情况,使用图案再认测验、配对学习测验和延迟匹配测验评定视觉记忆改善情况,使用反应时测验和斯特鲁普色词测验评定工作记忆改善情况,使用汉密尔顿抑郁量表(HAMD-17)评定疗效.结果 两组患者的空间工作记忆测验、图案再认测验、配对学习测验和斯特鲁普色词测验成绩在治疗后显著提高(P<0.05或P<0.01),A组的延迟匹配测验成绩显著高于B组(P<0.05),治疗时间因素和药物分组因素在数字广度测验和配对学习测验成绩上的交互作用显著(P<0.05或P<0.01).结论 文拉法辛和舍曲林对抑郁症患者工作记忆、视觉记忆和心理加工速度方面的认知功能均有一定改善作用,文拉法辛改善工作记忆和视觉记忆的作用比舍曲林更明显. 相似文献
8.
S. Ruotsalainen Ewen MacDonald Riitta Miettinen Tarja Puumala Paavo Riekkinen Sr. Jouni Sirviö 《Psychopharmacology》1997,130(4):303-312
The role of serotonin (5-HT) and its interaction with the muscarinic or nicotinic receptor-mediated mechanisms in the modulation
of working memory and motor activity was investigated by assessing the effects of 5-HT lesion and cholinergic receptor blockade
on the performance of rats in a working memory (delayed non-matching to position, DNMTP) task. A global serotonergic lesion
was induced by the intracerebroventricular adminstration of 5,7-dihydroxytryptamine (5,7-DHT). Post-mortem neurochemical analysis
revealed that serotonin and 5-hydroxyindoleacetic acid (5-HIAA) levels were reduced in frontal and parieto-occipital cortices
and in hippocampi of 5,7-DHT lesioned rats. 5-HIAA levels were also reduced in striatum. 5,7-DHT lesion slightly impaired
choice accuracy of rats in the DNMTP task and also transiently reduced motor activity in rats. Even the lower dose of scopolamine
(0.075 mg/kg), a muscarinic receptor antagonist, impaired the choice accuracy already at the shortest delay (i.e. not indicative
of a working memory impairment per se), and caused a marked disruption of motor activity (lengthened response latencies, increased
probability of omissions and decreased trials completed). Furthermore, the quaternary analogue, N-methylscopolamine (0.150 mg/kg), affected the motor activity of rats to the same extent as scopolamine. Mecamylamine (1.0;
3.0 mg/kg) also interfered with motor activity and it slightly decreased the choice accuracy, which was not dependent on the
delay. Although mecamylamine disrupted the performance of rats in the DNMTP task, the disruption was not as severe as that
seen with scopolamine. Moreover, both scopolamine and mecamylamine augmented the slight impairment on the choice accuracy
of 5,7-DHT lesioned rats, but this was non-mnemonic in character. We conclude that there is no evidence for any major interaction
between the serotonergic system and muscarinic or nicotinic cholinergic mechanisms in working memory per se, but muscarinic
and nicotinic receptor antagonists may act additively with the 5,7-DHT lesion to disrupt the choice accuracy of rats.
Received: 22 November 1995 / Final version: 25 November 1996 相似文献
9.
T. Kondo Osamu Tanaka Koichi Otani Kazuo Mihara Noboru Tokinaga Sunao Kaneko K. Chiba Takashi Ishizaki 《Psychopharmacology》1996,127(4):311-314
Effects of smoking and cytochrome P450 2C19 (CYP2C19) status on the single dose kinetics of zotepine and pharmacokinetic
interaction between zotepine and diazepam were investigated. In 14 healthy volunteers, the pharmacokinetics of zotepine after
a single oral 25 mg dose were compared between eight smokers and six non-smokers, or between seven extensive metabolizers
(EMs) and seven poor metabolizers (PMs) of S-mephenytoin. There was no significant difference in any pharmacokinetic parameters between smokers and non-smokers, or between
the EM and PM groups. In 17 patients treated with zotepine 80–340 mg/day, intra-individual changes in plasma concentrations
of zotepine caused by coadministration of diazepam 10 mg/day for 2 weeks were examined. Plasma concentrations of zotepine
were significantly increased after coadministration of diazepam (P < 0.05). Consequently, it is suggested that neither smoking nor CYP2C19 status affects the metabolism of zotepine. The elevation
in plasma concentrations of zotepine after coadministration of diazepam may be a result of competitive inhibition of zotepine
metabolism by diazepam via other isoenzyme than CYP2C19, e.g., CYP3A4.
Received: 25 March 1996/Final version: 28 May 1996 相似文献
10.
Scopolamine and lorazepam both produce anterograde impairments of explicit memory but only lorazepam impairs implicit memory
as assessed by perceptual priming tasks. The main aim of the two experiments reported in this article was to determine the
effects of these drugs on conceptual priming. Experiment 1 compared the effects of lorazepam (1,2 mg PO) with scopolamine
(0.3,0.6 mg SC) and placebo in a study with 60 healthy volunteers. Experiment 2 compared the separate and combined effects
of lorazepam (2 mg PO) and flumazenil (2 mg IV) with placebo in a study with 48 healthy volunteers. We found that conceptual
priming in category generation tasks was intact following lorazepam in both studies. This preservation of conceptual priming
contrasted with lorazepam-induced impairments on explicit memory tasks. In conjunction with previous findings, these results
are interpreted as providing further support for the notion that conceptual and perceptual priming are subserved by distinct
memory systems, one based on the operations of semantic memory, the other possibly based on a perceptual representation system.
That lorazepam impairs perceptual but not conceptual priming suggests that the neurochemical substrates of the two kinds of
priming are distinct.
Received: 10 December 1997/Final version: 27 April 1998 相似文献
11.
The effects of several centrally active drugs were investigated using two visual discrimination tasks: a two-lever food-rewarded conditional brightness discrimination, and a similar conditional brightness discrimination where a delay was introduced between the disappearance of the stimulus and the opportunity to respond on the levers for food. The substances tested (amphetamine, scopolamine, methylscopolamine, physostigmine, diazepam and-carboline benzodiazepine receptor antagonist, ZK 93426), all produced differing profiles of action on the performance parameters recorded. In the simple conditional visual discrimination, amphetamine increased omissions without significant effects on accuracy or response latency. Physostigmine enhanced response latencies and failures to respond without significant effects on accuracy. ZK 93426 had no consistent effects on accuracy although at higher doses, some increase in response latency was seen in the delayed responding version of the visual discrimination task. Diazepam had negative effects on all parameters in both discrimination procedures. Scopolamine disrupted responding, but not accuracy in the simple discrimination, whereas accuracy was reduced in a dose, but not delay dependent manner in the delayed discrimination. A similar effect to that observed with scopolamine was observed following methylscopolamine in the delayed discrimination procedure. In the simple visual discrimination small increases in accuracy were recorded, accompanied by increased response latencies. 相似文献
12.
Methcathinone (“CAT”) is a CNS stimulant that is a very significant drug of abuse in the former Soviet Union. It has also
appeared on the clandestine market in the United States and has been recently classified as a Schedule I substance. In the
present study, S(−)-methcathinone [S(−)-CAT, 0.50 mg/kg, IP] was employed as the training drug in a two-lever drug discrimination task in rats. Once established,
the S(−)-CAT stimulus was shown to have a rapid onset to action (within 5 min) and a duration of effect of approximately 60–90 min.
In tests of stimulus generalization (substitution), the S(−)-CAT (ED50 = 0.11 mg/kg) stimulus generalized to S(+)-methamphetamine (ED50 = 0.17 mg/kg), S(−)-cathinone (ED50 = 0.19 mg/kg), S(+)-amphetamine (ED50 = 0.23 mg/kg), aminorex (ED50 = 0.27 mg/kg), (±)-CAT (ED50 = 0.25 mg/kg), (±)-cathinone (ED50 = 0.41 mg/kg), R(+)-CAT (ED50 = 0.43 mg/kg), cis-4-methylaminorex (ED50 = 0.49 mg/kg), methylphenidate (ED50 = 0.83 mg/kg), and cocaine (ED50 = 1.47 mg/kg). S(−)-CAT-stimulus generalization did not occur to fenfluramine, a structurally related nonstimulant anorectic. Lastly, haloperidol
(AD50 = 0.18 mg/kg), a dopamine receptor antagonist, potently antagonized the S(−)-CAT stimulus. It is concluded that S(−)-methcathinone is a very potent CNS stimulant, which appears to produce its stimulus effect, at least in part, via a dopaminergic
mechanism.
Received: 4 August 1997/Final version: 27 March 1998 相似文献
13.
Rationale Recent psychopharmacological studies lend support to the notion of partially dissociable neuronal systems dedicated to processing specific emotions. For example, GABA-ergic enhancement after an acute dose of the benzodiazepine, diazepam, produces specific impairments in anger and fear recognition. However, it is unclear if these impairments are a general property of benzodiazepines and other drugs that produce a similar profile of neurocognitive impairment to benzodiazepines, such as the anticholinergic, scopolamine.Objective We investigated the effects of scopolamine and the benzodiazepine, lorazepam, on emotion-recognition accuracy.Methods A double-blind independent group design was used with 48 healthy volunteers to compare the effects of scopolamine and lorazepam with an inactive placebo on a commonly used emotion-recognition task. Control measures included an episodic memory task and subjective mood ratings.Results Anger and disgust recognition accuracy was impaired after scopolamine. In contrast, lorazepam produced no impairment in emotion-recognition despite producing similar levels of sedation and anterograde amnesia to scopolamine.Conclusions Scopolamine-induced cholinergic hypofunction selectively impaired the recognition accuracy of disgust and anger facial expressions. The effects of scopolamine on emotion-recognition are similar to those found in Huntington’s disease patients. Furthermore, the impairments in anger and fear recognition previously observed with diazepam do not appear to be a general property of benzodiazepines. This suggests that alterations in emotional processing involving changes in the ability to recognize threat-related emotions (particularly, fear and anger) may not be a principal mechanism underlying anxiolysis or paradoxical aggression seen with benzodiazepines. 相似文献
14.
Five pigeons were tested in a delayed matching-to-sample task after receiving an acute injection of DDAVP(1-desamino-8-D-arginine), scopolamine or d-amphetamine. A feeding test also was used to document non-specific drug effects. Scopolamine produced a marked dose-related decrement in accuracy of matching, regardless of delay, indicating that scopolamine impairs both discrimination and short-term memory. Neither DDAVP nor d-amphetamine produced consistent changes in delayed matching. Thus, an experimental model of short-term memory with pigeons did not confirm the findings of others of a positive effect of DDAVP upon cognitive performance in humans. 相似文献
15.
A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats. NAN-190 increased the latency to respond and reduced the number of nose pokes made during the delays in scopolamine-treated rats, and tended to potentiate the scopolamine-induced accuracy impairment. 1-PP did not affect the performance of scopolamine treated rats. Taken together, these results suggest that modulation of 5-HT1A receptors influences short term spatial working memory in the rat. 相似文献
16.
van Ruitenbeek P Vermeeren A Riedel W 《Journal of psychopharmacology (Oxford, England)》2008,22(6):663-672
Results from recent animal studies suggest an important role for histamine in memory functioning. Histaminergic drugs might prove beneficial for people suffering from memory impairment. To determine if histamine is involved in memory functioning this study evaluates the effects of histaminergic dysfunction on memory performance by administrating a H(1)-antagonist to humans. The study was conducted according to a 4-way, double-blind, crossover design in 20 healthy female volunteers, aged 18-45 years. On each test day subjects completed three test sessions: before and around 2 and 4 h after administration of single oral doses of dexchlorpheniramine 2 mg or 4 mg, scopolamine 1 mg or placebo. Drug effects were assessed using tests of memory, psychomotor and attention performance, and subjective alertness. Results showed that dexchlorpheniramine impaired performance in tests of spatial learning, reaction time, tracking and divided attention but showed no effects on working memory, visual memory, word learning or memory scanning. Scopolamine induced a similar pattern of effects. In addition, both drugs decreased subjective alertness. In conclusion results show that dexchlorpheniramine and scopolamine clearly impaired performance on psychomotor and attention tasks but do not suggest a specific role of the histaminergic system in learning and memory in humans. 相似文献
17.
Duka T Edelmann V Schütt B Dorow R Fichte K 《Journal of psychopharmacology (Oxford, England)》1992,6(3):382-388
It has been suggested from pharmacological studies in animals that ZK 93426 may improve memory and other cognitive processes in humans. Scopolamine has been used to model aspects of memory impairment. To test the effects of ZK 93426 alone and in combination with scopolamine, ZK 93426 (0.04 mg/kg) or vehicle (Intralipid R) was administered intravenously (i.v.) to normal controls, pre-treated with either scopolamine 0.5 mg administered subcutaneously (s.c.) or the same volume of saline. A visual (presentation of pictures) and a verbal (words list) memory test were applied. Both drugs on their own and in combination were found to be safe and well tolerated. ZK 93426 did not antagonize the scopolamine-induced impairment of acquisition of the words list. Scopolamine did not impair delayed recall of visual or verbal material. ZK 93426 alone improved performance in delayed recall of visual material presented after drug application, whereas it impaired performance in delayed recall of visual material presented before drug administration. 相似文献
18.
The present study was conducted to determine the degree to which impairments in attention accompany the memory deficits produced by scopolamine. Eighteen healthy young volunteers received scopolamine 0·6 mg subcutaneously on three experimental sessions and placebo on three others. On each session, prior to, and 60 min after injection, the subjects underwent an automated computerized battery of 11 cognitive tasks. The study was run double-blind and the order of treatment conditions over successive visits was counterbalanced between subjects. Scopolamine produced marked and significant decrements on all major aspects of performance from the battery. The drug lowered the efficiency of the detection and processing of information in tests of visual vigilance, rapid information processing, choice reaction, letter cancellation and logical reasoning. These effects were accompanied by a lowering of critical flicker-fusion frequency and subjective alertness. Memory was also impaired on tests of immediate recall, delayed recall, recognition and memory scanning. These findings confirm and extend previous work, demonstrating that scopolamine impairs the selection and evaluation of environmental information, as well as reducing the likelihood of information being subsequently recalled or recognized. Whether the former effects contribute to the latter is not known, but this must be considered a possibility. This potential role of processing deficits in memory loss associated with cholinergic blockade is briefly considered in relation to the cholinergic hypothesis of geriatric memory loss. 相似文献
19.
D. O. Stichtenoth D. Tsikas F.-M. Gutzki J. C. Frölich 《European journal of clinical pharmacology》1996,51(3-4):231-234
Objective:
In the present randomized, four-way crossover study we determined the effects of two oral doses each of ketoprofen and ibuprofen
on platelet aggregation and prostanoid formation in man.
Methods:
Twelve healthy female volunteers received for 2 consecutive days, followed by a 5-day drug-free interval, one of the following:
ketoprofen 3 × 25 mg per day, or ketoprofen 3 × 50 mg per day, or ibuprofen 3 × 200 mg per day, or ibuprofen 3 × 400 mg per
day. The response criteria, determined before and on the 2nd day of each treatment period, were: maximal platelet aggregation
in response to 1.0 mmol ⋅ l–1 arachidonic acid measured by the method of Born and Cross, thromboxane B2 (TXB2) concentration in platelet-rich plasma after aggregation measured by radioimmunoassay, and PGE-M, the index metabolite of
total body prostaglandin E2 (PGE2) production, assessed by gas chromatography/tandem mass spectrometry using 18O2-PGE-M as internal standard.
Results:
Platelet aggregation was significantly reduced by ketoprofen 3 × 25 mg per day (−57%) and ketoprofen 3 × 50 mg per day (−85%)
as compared to control, whereas ibuprofen 3 × 200 mg per day (−3%) and ibuprofen 3 × 400 mg per day (−22%) had no significant
effects. TXB2 synthesis was significantly decreased by ketoprofen 3 × 25 mg per day (−72%), ketoprofen 3 × 50 mg per day (−97%) and ibuprofen
3 × 400 mg per day (−48%) as compared to control; ibuprofen 3 × 200 mg per day did not reduce TXB2 formation significantly (−23%). All four treatments reduced 24-h urinary excretion of PGE-M significantly in the range of−39%
(ketoprofen 3 × 25 mg per day) to −53% (ibuprofen 3 × 400 mg per day) without significant differences between treatments.
Conclusion:
Our data show that both ketoprofen dosages were more effective in inhibition of platelet aggregation and platelet thromboxane
synthesis than ibuprofen in low or high dosage. Total body synthesis of the E-prostaglandins was inhibited by all drug schedules
without significant differences between treatments.
Received: 26 January 1996;/Accepted in revised form: 11 June 1996 相似文献
20.
I. Kantola A. Terént T. Honkanen V. Järveläinen K. Ekman M. Kataja 《European journal of clinical pharmacology》1996,50(3):155-159
Objective: To compare the safety, efficacy, tolerability and duration of the antihypertensive effect of an ACE-inhibitor spirapril
3 mg or 6 mg in elderly (≥ 60 y) hypertensive patients in a multicentre, observational, double-blind randomised study.
Methods:
After a four-week placebo period, 39 patients were randomised to six weeks of treatment with spirapril 3 mg and 47 patients
with spirapril 6 mg.
Results:
In the sitting position the mean (SD) decrease in systolic blood pressure (SBP) was 12(15) mmHg (95% confidence interval 7
to 17 mmHg) and in dia- stolic blood pressure (DBP) 10(7) mmHg (8 to 12 mmHg) in the 3-mg group and 10(13) mmHg (6 to 14 mmHg)
and 9(7) mmHg (7 to 11 mmHg), respectively, in the 6-mg group (P < 0.001 compared to placebo period in both groups). Spirapril 3mg and 6 mg produced DBP ≤ 90 mmHg or a fall ≥ 10 mmHg in 53%
and 51% of the patients, respectively. DBP was ≤ 90 mmHg in 36% and SBP ≤ 160 mmHg in 67% of the patients taking 3 mg and
in 26% and 63% of the patients taking 6 mg spirapril. The most commonly reported adverse effects were cough (13–17%), dizziness,
headache and insomnia. A trend to a more frequent adverse effects was observed in patients receiving spirapril 6 mg. Spirapril
was both cholesterol- and glucose-neutral.
Conclusion:
According to our study, spirapril 3mg seems to be a suitable starting dose for the treatment of hypertension in the elderly
patients.
Received: 8 August 1995/Accepted in revised form: 7 November 1995 相似文献