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1.
Akhondzadeh S Ghayyoumi R Rezaei F Salehi B Modabbernia AH Maroufi A Esfandiari GR Naderi M Ghebleh F Tabrizi M Rezazadeh SA 《Psychopharmacology》2011,213(4):809-815
Rational
It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia.Objective
This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial.Methods
Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45?years. All patients were inpatients and were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion: 20 to risperidone (6?mg/day) plus sildenafil (75?mg/day) and 20 to risperidone (6?mg/day) plus placebo. The principal measure of outcome was Positive and Negative Syndrome Scale (PANSS).Results
Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F?=?4.77, df?=?1; P?=?0.03; F?=?5.91, df?=?1, P?=?0.02 respectively).Conclusion
Therapy with 75?mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11). 相似文献2.
Stefan Jongen Eric Vuurman Jan Ramaekers Annemiek Vermeeren 《Psychopharmacology》2014,231(12):2435-2447
Rationale
Medication and illicit drugs can have detrimental side effects which impair driving performance. A drug’s impairing potential should be determined by well-validated, reliable, and sensitive tests and ideally be calibrated by benchmark drugs and doses. To date, no consensus has been reached on the issue of which psychometric tests are best suited for initial screening of a drug’s driving impairment potential.Objective
The aim of this alcohol calibration study is to determine which performance tests are useful to measure drug-induced impairment. The effects of alcohol are used to compare the psychometric quality between tests and as benchmark to quantify performance changes in each test associated with potentially impairing drug effects.Methods
Twenty-four healthy volunteers participated in a double-blind, four-way crossover study. Treatments were placebo and three different doses of alcohol leading to blood alcohol concentrations (BACs) of 0.2, 0.5, and 0.8 g/L.Results
Main effects of alcohol were found in most tests. Compared with placebo, performance in the Divided Attention Test (DAT) was significantly impaired after all alcohol doses and performance in the Psychomotor Vigilance Test (PVT) and the Balance Test was impaired with a BAC of 0.5 and 0.8 g/L. The largest effect sizes were found on postural balance with eyes open and mean reaction time in the divided attention and the psychomotor vigilance test.Conclusions
The preferable tests for initial screening are the DAT and the PVT, as these tests were most sensitive to the impairing effects of alcohol and being considerably valid in assessing potential driving impairment. 相似文献3.
Smith WB Marbury TC Komjathy SF Sumeray MS Williams GC Hu MY Mould DR 《European journal of clinical pharmacology》2012,68(10):1385-1394
Purpose
Clevidipine is a rapidly-acting intravenous dihydropyridine antihypertensive acting via calcium channel blockade. This was a randomized, single-blind, parallel-design study of a 72-h continuous clevidipine infusion.Method
Doses of 2, 4, 8, or 16.0?mg/h or placebo were evaluated in 61 subjects with mild to moderate essential hypertension. IV clevidipine or placebo was initiated at 2.0?mg/h and force-titrated in doubling increments every 3?min to target dose, then maintained for 72?h. Blood pressure and heart rate were measured during infusion, and for 4, 6 and 8?h after termination of infusion, although oral therapy could be restarted at 4?h. Clevidipine blood levels were obtained during infusion and for 1?hour after termination.Results
Rapid onset of drug effect occurred at all clevidipine dose levels, with consistent pharmacokinetics and rapid offset after 72-h infusion. No evidence of tolerance to the clevidipine drug effect was observed at any dose level over the 72-h infusion. No evidence of rebound hypertension was found for either 4 or 6?h after termination of the clevidipine infusion. At 8?h following cessation of clevidipine, blood pressure was not significantly higher than at baseline. Placebo-treated subjects had blood pressures lower than baseline at 8?h following infusion termination; hence, placebo-adjusted blood pressures tended to be slightly higher than baseline.Conclusion
This study supports the use of up to 72?h of IV clevidipine therapy for the management of blood pressure, with consistent pharmacokinetic/pharmacodynamic characteristics and context insensitive half-life across the dose ranges evaluated. 相似文献4.
Oltmanns KM Heldmann M Daul S Klose S Rotte M Schäfer M Heinze HJ Münte TF Lehnert H 《Psychopharmacology》2012,221(4):693-700
Rationale
Sibutramine, a centrally-acting selective monoamine reuptake inhibitor, has been used as an appetite suppressant drug in obesity.Objectives
To gain insight into the central nervous actions of sibutramine, brain responses to pictures of food items after sibutramine vs placebo application were assessed by functional magnetic resonance imaging (fMRI) in obese women.Methods
In a randomized double-blind crossover design, 10 healthy obese women (BMI 31.8–39.9?kg/m2) received 15?mg/d of sibutramine vs placebo for 14?d. Obese participants, and a group of 10 age-matched normal weight controls, viewed pictures of food items and control objects in hungry and satiated states while lying in the MR scanner. The paradigm followed a block design. In obese participants, fMRI measurements were conducted prior and after two weeks of daily sibutramine or placebo administration, whereas control participants were scanned only at one point in time.Results
Upon food item presentation, obese participants showed increased brain activity in areas related to emotional and reward processing, perceptual processing, and cognitive control as compared to normal weight controls. Sibutramine exerted a divergent satiety-dependent effect on amygdala activity in obese participants, increasing activity in the hungry state while decreasing it under conditions of satiation.Conclusions
Our results demonstrate a modulatory influence of sibutramine on amygdala activity in obese women which may underlie the appetite suppressant effects of the drug. 相似文献5.
Anne Schmechtig Jane Lees Lois Grayson Kevin J. Craig Rukiya Dadhiwala Gerard R. Dawson J. F. William Deakin Colin T. Dourish Ivan Koychev Katrina McMullen Ellen M. Migo Charlotte Perry Lawrence Wilkinson Robin Morris Steve C. R. Williams Ulrich Ettinger 《Psychopharmacology》2013,227(2):331-345
Rationale
The increasing demand to develop more efficient compounds to treat cognitive impairments in schizophrenia has led to the development of experimental model systems. One such model system combines the study of surrogate populations expressing high levels of schizotypy with oculomotor biomarkers.Objectives
We aimed (1) to replicate oculomotor deficits in a psychometric schizotypy sample and (2) to investigate whether the expected deficits can be remedied by compounds shown to ameliorate impairments in schizophrenia.Methods
In this randomized double-blind, placebo-controlled study 233 healthy participants performed prosaccade (PS), antisaccade (AS) and smooth pursuit eye movement (SPEM) tasks after being randomly assigned to one of four drug groups (nicotine, risperidone, amisulpride, placebo). Participants were classified into medium- and high-schizotypy groups based on their scores on the Schizotypal Personality Questionnaire (SPQ, Raine (Schizophr Bull 17:555–564, 1991)).Results
AS error rate showed a main effect of Drug (p?<?0.01), with nicotine improving performance, and a Drug by Schizotypy interaction (p?=?0.04), indicating higher error rates in medium schizotypes (p?=?0.01) but not high schizotypes under risperidone compared to placebo. High schizotypes had higher error rates than medium schizotypes under placebo (p?=?0.03). There was a main effect of Drug for saccadic peak velocity and SPEM velocity gain (both p?≤?0.01) indicating impaired performance with risperidone.Conclusions
We replicate the observation of AS impairments in high schizotypy under placebo and show that nicotine enhances performance irrespective of group status. Caution should be exerted in applying this model as no beneficial effects of antipsychotics were seen in high schizotypes. 相似文献6.
Mehdi Farokhnia Maryam Sabzabadi Hossein Pourmahmoud Mohammad-Reza Khodaie-Ardakani Seyed-Mohammad-Reza Hosseini Habibeh Yekehtaz Mina Tabrizi Farzin Rezaei Bahman Salehi Shahin Akhondzadeh 《Psychopharmacology》2014,231(3):533-542
Rationale
Several recent studies have focused on glutamate modulating agents for symptoms relief in schizophrenia, especially negative symptoms which are resistant to conventional therapies.Objectives
We aimed to assess the efficacy and tolerability of riluzole, an anti-glutamate agent with neuroprotective properties, as an adjunct to risperidone in improving negative symptoms of schizophrenia.Methods
In this randomized double-blind placebo-controlled parallel-group study, 50 patients with chronic schizophrenia and a score of ≥20 on the negative subscale of positive and negative syndrome scale (PANSS) were enrolled in the active phase of their illness. Participants were equally randomized to receive riluzole (100 mg/day) or placebo in addition to risperidone (up to 6 mg/day) for 8 weeks. Participants were rated by PANSS every 2 weeks. The primary outcome of this study was the difference in the decrease of PANSS negative subscale score from baseline to the study endpoint between the two groups.Results
By the study endpoint, riluzole-treated patients showed significantly greater improvement in the negative symptoms (P?<?0.001) as well as the PANSS total and general psychopathology subscale scores (P?=?0.001 and P?<?0.001; respectively) compared to the placebo group. Treatment group was the only significant predictor of changes in negative symptom in this trial (β?=??0.56, P?<?0.001). No significant difference was observed between two groups in the frequency of side effects.Conclusion
These preliminary findings suggest that riluzole may be a safe and effective medication for the treatment of negative symptoms in patients with chronic schizophrenia. Further research and replication of study findings is warranted.Clinical trial registry name and registration number
Iranian registry of clinical trials www.irct.ir, IRCT201107281556N26 相似文献7.
Rationale
The loudness dependence of the auditory evoked potential (LDAEP) is considered a noninvasive in vivo marker of central serotonergic functioning in humans. Nevertheless, results of genetic association studies point towards a modulation of this biomarker by dopaminergic neurotransmission.Objective
We examined the effect of dopaminergic modulation on the LDAEP using L-3,4-dihydroxyphenylalanine (levodopa)/benserazide (Madopar?) as a challenge agent in healthy volunteers.Methods
A double-blind placebo-controlled challenge design was chosen. Forty-two healthy participants (21 females and 21 males) underwent two LDAEP measurements, following a baseline LDAEP measurement either placebo or levodopa (levodopa 200?mg/benserazide 50?mg) were given orally. Changes in the amplitude and dipole source activity of the N1/P2 intensities (60, 70, 80, 90, and 100?dB) were analyzed.Results
The participants of neither the levodopa nor the placebo group showed any significant LDAEP alterations compared to the baseline measurement. The test?Cretest reliability (Cronbachs Alpha) between baseline and intervention was 0.966 in the verum group and 0.759 in the placebo group, respectively.Conclusions
The administration of levodopa showed no effect on the LDAEP. These findings are in line with other trials using dopamine receptor agonists. 相似文献8.
Rationale
An emerging literature associates increased dopaminergic neurotransmission with altered brain response to aversive stimuli in humans. The direction of the effect of dopamine on aversive motivation, however, remains unclear, with some studies reporting increased and others decreased amygdala activation to aversive stimuli following the administration of dopamine agonists. Potentiation of the startle response by aversive foreground stimuli provides an objective and directional measure of emotional reactivity and is considered useful as an index of the emotional effects of different drugs.Objective
We investigated the effects of two doses of d-amphetamine (5 and 10 mg), compared to placebo, for the first time to our knowledge, using the affect–startle paradigm.Method
The study employed a between-subjects, double-blind design, with three conditions: 0 mg (placebo), and 5 and 10 mg d-amphetamine (initially n?=?20/group; final sample: n?=?18, placebo; n?=?18, 5 mg; n?=?16, 10 mg). After drug/placebo administration, startle responses (eyeblinks) to intermittent noise probes were measured during viewing of pleasant, neutral and unpleasant images. Participants’ general and specific impulsivity and fear-related personality traits were also assessed.Results
The three groups were comparable on personality traits. Only the placebo group showed significant startle potentiation by unpleasant, relative to neutral, images; this effect was absent in both 5- and 10-mg d-amphetamine groups (i.e. the same effect of d-amphetamine observed at different doses in different people).Conclusions
Our findings demonstrate a reduced aversive emotional response under d-amphetamine and may help to account for the known link between the use of psychostimulant drugs and antisocial behaviour. 相似文献9.
Objective
The study aimed to assess, at trough plasma concentration, the anti-ischemic and antianginal efficacy and tolerability of trimetazidine modified release (MR) 35mg taken twice daily by patients with stable angina pectoris.Design
This multicenter, randomized, double-blind, placebo-controlled, international study started with a run-in period of 3 weeks with atenolol 50 mg/day and placebo, followed by a 6-month treatment period with once daily atenolol 50mg and twice daily trimetazidine MR 35mg or placebo.Patients
The study involved 223 patients with stable angina pectoris (class II or III of the Canadian Cardiovascular Society [CCS] classification). 180 patients were analyzed in the full analysis set (FAS) following the intention to treat principle (ITT) and 167 patients were analyzed in the per protocol set (PPS). The PPS data are presented here.Interventions
Two exercise tolerance tests (ETTs) were performed during the run-in period in order to assess the stability of exercise tolerance before angina pectoris and significant ST segment depression. Efficacy was assessed by a third ETT performed after 8 weeks of treatment, at trough, 12 hours after the intake of the drug. Safety was evaluated over the 6-month duration of the study.Main outcomes measures
Time to 1mm ST segment depression.Results
Time to 1mm ST segment depression was increased by 44 seconds more in the trimetazidine MR 35mg group than in the placebo group (p = 0.005). A significant difference was also evidenced for the time to onset of angina pectoris (p = 0.049) and for the reason for stopping the exercise (p = 0.02). No difference between groups was found for safety parameters.Conclusion
This study demonstrates the anti-ischemic and antianginal efficacy of trimetazidine MR 35mg twice daily at trough plasma concentrations in patients with stable angina pectoris receiving atenolol 50 mg/day. Furthermore, the drug is well tolerated over 6 months. 相似文献10.
Objective
Several studies have shown that glucocorticoids can impair declarative memory retrieval and working memory (WM) performance. The aim of the present study was to investigate the impact of a high dose of hydrocortisone on WM, as well as to examine the effects of cortisol suppression via treatment with a high dose of dexamethasone (DEX). We hypothesized that hydrocortisone treatment results in an impaired cognitive function compared with placebo. We further expected that dexamethasone treatment is also followed by cognitive impairment, due to the hypothesis that very low levels of cortisol are also associated with alterations in memory performance.Methods
In a placebo-controlled study with a within-subject design, 16 healthy volunteers received placebo or 120?mg of hydrocortisone (two boluses of 60?mg) directly before neuropsychological testing or 4?mg of DEX the day before testing.Results
We did not find any effect of hydrocortisone on WM and cognitive flexibility, even though cortisol levels were high at the time of testing. Furthermore, we did not find any effect of DEX treatment on WM and reaction time in a cognitive flexibility test. However, cognitive flexibility was negatively correlated with adrenocorticotropin (ACTH) in the DEX condition.Conclusions
Our results found no clear effect of hydrocortisone and dexamethasone treatment on WM. These results emphasize the need for further research on the association between hypothalamic?Cpituitary?Cadrenal axis activity and cognition. These studies should investigate the hypotheses of dose-dependent associations in more detail and should also include analyses on ACTH and cognition. 相似文献11.
Background and rationale
Nicotinic acetylcholine systems play major roles in cognitive function. Nicotine and a variety of nicotinic agonists improve attention, and nicotinic antagonist exposure impairs it. This study was conducted to investigate the effect of a novel nicotinic receptor agonist at ??4??2 nicotinic receptors (AZD3480) on attention and reversal of pharmacologically induced attentional impairment produced by the NMDA glutamate antagonist dizocilpine (MK-801).Methods
Adult female Sprague-Dawley rats were trained to perform an operant visual signal detection task to a stable baseline of accuracy. The rats were then injected subcutaneously following a repeated measures, counter-balanced design with saline, AZD3480 (0.01, 0.1, and 1 mg/kg), dizocilpine (0.05 mg/kg), or their combinations 30 min before the test. The effect of donepezil on the same pharmacologically induced attentional impairment was also tested. A separate group of rats was injected with donepezil (0.01, 0.1, and 1 mg/kg), dizocilpine (0.05 mg/kg), or their combinations, and their attention were assessed. Saline was the vehicle control.Results
Dizocilpine caused a significant (p?0.0005) impairment in percent correct performance. This attentional impairment was significantly (p?0.0005) reversed by 0.01 and 0.1 mg/kg of AZD3480. AZD3480 by itself did not alter the already high baseline control performance. Donepezil (0.01?C1.0 mg/kg) also significantly (p?0.005) attenuated the dizocilpine-induced attentional impairment.Conclusions
AZD3480, similar to donepezil, showed significant efficacy for counteracting the attentional impairment caused by the NMDA glutamate antagonist dizocilpine. Low doses of AZD3480 may provide therapeutic benefit for reversing attentional impairment in patients suffering from cognitive impairment due to glutamatergic dysregulation and likely other attentional disorders. 相似文献12.
Peter Kranke Kerstin D. R?hm Pierre Diemunsch Tong J. Gan Christian C. Apfel Leopold Eberhart Harold S. Minkowitz Jan Wallenborn Dominique Chassard Gilles Lebuffe Gabriel M. Fox Martin R. Tramèr 《European journal of clinical pharmacology》2012,68(11):1465-1472
Rationale
Buspirone, a partial 5HT1A agonist and D2 and D3 antagonist, has shown promising antiemetic efficacy when given parenterally in animal models, but its efficacy for the prevention of postoperative nausea and vomiting (PONV) is unknown.Objective
To study the efficacy and dose-responsiveness of intravenous buspirone for the prevention of PONV.Methods
A randomised, double-blind, placebo-controlled study was performed in adults at moderate to high PONV risk undergoing surgery with a general anaesthetic. Patients were randomised to receive an intravenous dose of buspirone (0.3, 1.0, 2.0, 3.0?mg) or placebo at the end of surgery. The primary endpoint was the cumulative 24-h PONV incidence (i.e. any nausea and/or vomiting). Vomiting included retching. Nausea was defined as a score of ≥4 on an 11-point verbal rating scale running from zero (no nausea) to ten (the worst nausea imaginable).Results
A total of 257 patients received the study drug and fulfilled the criteria for inclusion in the primary efficacy and safety analyses. With placebo, the mean 24-h PONV incidence was 49.0?% (90?% confidence interval [CI] 37.5–60.5?%). With buspirone, that incidence ranged from a mean of 40.8?% (29.3–52.4?%) in the 1?mg arm to 58.0?% (46.5–69.5?%) in the 0.3?mg arm (P?>?0.05 for all comparisons). There was no difference between placebo and buspirone at any dose for any other efficacy endpoint, nor in the number or severity of adverse events or any other safety measures.Conclusion
We were unable to show that intravenous single-dose buspirone, at the tested dose-range, was effective at preventing PONV in surgical adult patients. The present study emphasises the difficulty in extrapolating from animal models of emesis to clinical efficacy in PONV. 相似文献13.
14.
Nicolas LB Gutierrez MM Binkert C Dingemanse J 《European journal of clinical pharmacology》2012,68(9):1257-1266
Purpose
To evaluate the pharmacokinetics, pharmacodynamics, safety, and tolerability of escalating single oral doses of ACT-077825, a novel orally active renin inhibitor, in healthy male subjects.Methods
In this single-center, double-blind, placebo- and active-controlled (with enalapril) randomized study, 70 subjects received a single dose of ACT-077825 (1–1,000?mg), placebo, or enalapril 20?mg under fasted conditions. The main pharmacokinetic endpoints were area under the plasma ACT-077825 concentration–time curve from time zero to infinity and the terminal half-life (t1/2). The pharmacodynamic endpoints included immunoactive active renin (iAR) plasma concentrations and plasma renin activity (PRA). Standard laboratory and safety data were collected.Results
Of the few adverse events reported, diarrhea and headache were the most frequent. The pharmacokinetics of ACT-077825 were dose-proportional in the dose range 100 to 1,000?mg. Terminal t1/2, best characterized following a dose of 1,000?mg, was 41.6?h and tmax 4–5?h post-dose. ACT-077825 dose-dependently increased iAR and decreased PRA, effects that were associated with a decrease in blood pressure at 1,000?mg, similar to following treatment with enalapril.Conclusion
The results provide evidence that ACT-077825, with a pharmacokinetic profile consistent with a once-a-day dosing regimen, may represent an effective antihypertensive agent and pave the way toward a multiple-ascending dose study. 相似文献15.
Cho W Maruff P Connell J Gargano C Calder N Doran S Fox-Bosetti S Hassan A Renger J Herman G Lines C Verma A 《Psychopharmacology》2011,218(3):513-524
Rationale
Enhancement of histaminergic neurotransmission or histaminergic plus cholinergic neurotransmission may represent novel strategies for improving cognition in Alzheimer's disease.Objective
To evaluate the effects of a novel histamine H3 receptor inverse agonist (MK-3134), an acetylcholinesterase inhibitor (donepezil), and their combination in attenuating the cognitive impairment associated with scopolamine.Methods
Thirty-one subjects were randomized, and 28 completed this double-blind, placebo-controlled, five-period crossover study. Cognition was assessed using the Groton Maze Learning Task (GMLT) as the primary outcome measure. The two primary hypotheses were that donepezil 10?mg and MK-3134 25?mg, respectively, would attenuate scopolamine (0.5?mg)-induced impairment as measured by the GMLT over the first 12?h after scopolamine administration (AUC1?C12? h). A secondary hypothesis was that the combination of donepezil and MK-3134 would attenuate scopolamine-induced cognitive impairment to a greater extent than either agent alone as measured by the GMLT AUC1?C12?h.Results
The primary and secondary hypotheses were not met. Upon examining the time course of the scopolamine effects (an exploratory objective), peak effects were generally observed around 2?h after scopolamine administration. Administration of MK-3134 or donepezil improved performance on the GMLT at the 2-h time point, rather than AUC1?C12?h, compared with scopolamine alone. Moreover, it appeared that the combination of MK-3134 and donepezil blunted the scopolamine effect to a greater extent than either drug alone.Conclusions
Exploratory analyses provide evidence for cognitive improvement through inverse agonism of the H3 histamine receptor and for cooperation between human cholinergic and histaminergic neurotransmitter systems. (ClinicalTrials.gov trial registration number: NCT01181310) 相似文献16.
Mahtab Asadabadi Mohammad-Reza Mohammadi Ahmad Ghanizadeh Amirhossein Modabbernia Mandana Ashrafi Elmira Hassanzadeh Saeedeh Forghani Shahin Akhondzadeh 《Psychopharmacology》2013,225(1):51-59
Rational
Autism is associated with activation of the inflammatory response system.Objective
This study aims to assess the efficacy of a cyclooxygenase-2 inhibitor, celecoxib, as adjunctive therapy in the treatment of autismMethods
In a 10-week randomized double-blind placebo-controlled study, 40 outpatient children with a Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision clinical diagnosis of autism were randomly allocated to celecoxib plus risperidone or placebo plus risperidone. The dose of risperidone and celecoxib were titrated up to 3 and 300 mg/day, respectively. Patients were assessed at baseline and after 2, 4, 6, and 10 weeks of starting medication using the Aberrant Behavior Checklist-Community (ABC-C) Rating Scale. Primary outcome measure was the change in irritability subscale of ABC-C.Results
Significant time?×?treatment interaction was observed for Irritability (F (1.658, 63.021)?=?13.580, P?<?0.001), Lethargy/Social Withdrawal (F (1.948, 74.032)?=?16.811, P?<?0.001), and Stereotypic Behavior (F(1.742, 66.198)?=?12.104, P?<?0.001), but not for Hyperactivity/Noncompliance (F (2.564, 97.424)?=?1.469, P?=?0.232), and Inappropriate Speech subscales (F (1.607, 61.075)?=?0.173, P?=?0.794). By week 10, patients in the celecoxib group showed significantly greater improvement in the Irritability (P?<?0.001), Lethargy/Social Withdrawal (P?<?0.001), and Stereotypic Behavior (P?<?0.00) but not in Hyperactivity/Noncompliance (P?=?0.202) and Inappropriate Speech (P?=?0.802) subscales than the placebo group. Complete response was achieved by four (20 %) patients in the placebo group and 11 (55 %) patients in the celecoxib group (χ 2 (1)?=?5.227, P?=?0.022). Frequency of side effects was similar between the two groups.Conclusions
Combination of risperidone and celecoxib was superior to risperidone alone in treating irritability, social withdrawal, and stereotypy of children with autism. (Registration, www.irct.ir; IRCT138711091556N2) 相似文献17.
Rationale
Performance on the Cambridge Neuropsychological Test Automated Battery touchscreen paired-associates learning (PAL) test is predictive of Alzheimer??s disease and impaired in schizophrenia and chronic drug users. An automated computer touchscreen PAL task for rats has been previously established. A pharmacologically validated PAL task for mice would be a highly valuable tool, which could be useful for a number of experimental aims including drug discovery.Objectives
This study sought to investigate the effects of systemic administration of cholinergic agents on task performance in C57Bl/6 mice.Methods
Scopolamine hydrobromide (0.02, 0.2, and 2.0?mg/kg), dicyclomine hydrochloride (M1 receptor antagonist; 2.0, 4.0, and 8.0?mg/kg), and donepezil hydrochloride (cholinesterase inhibitor; 0.03, 0.1, and 0.3?mg/kg) were administered post-acquisition in C57Bl/6 mice performing the PAL task.Results
Scopolamine (0.2 and 2.0?mg/kg) and dicyclomine (at all administered doses) significantly impaired PAL performance. A significant facilitation in PAL was revealed in mice following donepezil administration (0.3?mg/kg).Conclusions
The present study shows that mice can acquire the rodent PAL task and that the cholinergic system is important for PAL task performance. M1 receptors in particular are likely implicated in normal performance of PAL. The finding that mouse PAL can detect both impairments and improvements indicates that this task could prove to be a highly valuable tool for a number of experimental aims including drug discovery. 相似文献18.
T. R. M. Leufkens J. G. Ramaekers A. W. de Weerd W. J. Riedel A. Vermeeren 《Psychopharmacology》2014,231(14):2785-2798
Rationale
Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs.Objectives
The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls).Methods
The study was conducted according to a 3?×?2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test.Results
Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls.Conclusions
The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients. 相似文献19.
Dr Waymon Drummond Y. M. Sirenko E. Ramos I. Baek D. L. Keefe 《Am J Cardiovasc Drugs》2011,11(5):327-333
Background
Hypertension frequently coexists with diabetes mellitus, resulting in increased cardiovascular risk. Thus, BP control is crucial in decreasing morbidity and mortality in this difficult-to-treat patient population.Objective
The objective of this study was to evaluate the efficacy and safety of aliskiren in hypertensive patients with diabetes not adequately responsive to the combination of valsartan and hydrochlorothiazide (HCT).Methods
After a 1-to 4-week washout period, patients with a mean sitting diastolic BP (msDBP) ≥95mmHg were treated with valsartan 160mg for 2 weeks followed by valsartan/HCT 160mg/25mg for an additional 4 weeks (single-blind active run-in period). Patients whose msDBP remained ≥85mmHg after the active run-in period were randomized (1 : 1) to receive aliskiren 150mg (n = 184) or placebo (n = 179) as add-on therapy for 6 weeks. Aliskiren was then force-titrated to 300mg once daily for another 6 weeks. Efficacy variables were: the change in msDBP and mean sitting systolic BP (msSBP) from baseline to week 12 endpoint, diastolic response (msDBP < 80mmHg or reduction of at least 10mmHg), and BP control rate (<130/80mmHg).Results
Of the 363 patients randomized, 328 (90.4%) completed the study (aliskiren and placebo groups: 89.7% and 91.1%, respectively). At week 12 endpoint, the least squares mean (LSM) changes in msDBP (aliskiren vs placebo: ?5.8 vs ?4.8mmHg; p = 0.2767) and msSBP (aliskiren vs placebo: ?7.3 vs ?4.8 mmHg; p = 0.0725) were numerically greater in patients treated with aliskiren compared with those treated with placebo; however, this difference was not statistically significant. The proportion of diastolic responders (aliskiren and placebo: 68.5% and 72.9%, respectively; p = 0.8482) and patients achieving BP control (aliskiren and placebo: 16.0% and 16.4%, respectively; p = 0.7511) were similar for both groups. Overall, 63 (34%) and 59 (33%) patients in the aliskiren and placebo groups, respectively, experienced adverse events (AEs). The most commonly reported AEs were headache (placebo group: 6.1%) and dizziness (aliskiren group: 4.4%). Aliskiren was well tolerated.Conclusion
The reductions in BP with aliskiren added to valsartan/HCT in this study were numerically greater compared with placebo added to valsartan/HCT, although not statistically significant. Trial Registration: ClinicalTrials.gov identifier NCT00219102. 相似文献20.
Maryam Noroozian Sina Ghasemi Seyed-Mohammad-Reza Hosseini Amirhossein Modabbernia Mohammad-Reza Khodaie-Ardakani Omid Mirshafiee Mehdi Farokhnia Masih Tajdini Farzin Rezaei Bahman Salehi Mandana Ashrafi Habibeh Yekehtaz Mina Tabrizi Shahin Akhondzadeh 《Psychopharmacology》2013,228(4):595-602