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31.
M Mantovani DJ Dooley A Weyerbrock R Jackisch TJ Feuerstein 《British journal of pharmacology》2009,158(7):1848-1856
Background and purpose:
Although the amino acid sequences of rat and human 5-hydroxytryptamine (5-HT) and noradrenaline (NA) transporters (i.e. SERT and NET) are highly homologous, species differences exist in the inhibitory effects of drugs acting at these transporters. Therefore, comparison of the potencies of drugs acting at SERT and NET in native human and rat neocortex may serve to more accurately predict their clinical profile.Experimental approach:
Synaptosomes prepared from fresh human and rat neocortical tissues were used for [3H]-5-HT and [3H]-NA saturation and competition uptake experiments. The drugs tested included NA reuptake inhibitors (desipramine, atomoxetine and (S,S)-reboxetine), 5-HT reuptake blockers (citalopram, fluoxetine and fluvoxamine) and dual 5-HT/NA reuptake inhibitors (duloxetine and milnacipran).Key results:
In saturation experiments on synaptosomal [3H]-5-HT and [3H]-NA uptake, the dissociation constants did not indicate species differences although a smaller density of both SERT and NET was observed in human tissues. In competition experiments with the various drugs, marked species differences in their potencies were observed, especially at SERT. The rank order of selectivity ratios (SERT/NET) in human neocortex was as follows: citalopram ≥ duloxetine = fluvoxamine ≥ fluoxetine > milnacipran > desipramine = atomoxetine > (S,S)-reboxetine. Significant species differences in these ratios were observed for duloxetine, atomoxetine and desipramine.Conclusions and implications:
This study provides the first compilation of drug potency at native human neocortical SERT and NET. The significant species differences (viz., human vs. rat) in drug potency suggest that the general use of rodent data should be limited to predict clinical efficacy or profile. 相似文献32.
The aim of the present study was to investigate the possible effects of antidepressant drugs (fluvoxamine, imipramine) on the metabolism of the aliphatic-type phenothiazine neuroleptic chlorpromazine in the human liver. The experiment was performed in vitro using human liver microsomes. The kinetic analysis of chlorpromazine metabolism carried out in the absence or presence of antidepressants showed that fluvoxamine potently inhibited chlorpromazine 5-sulfoxidation (K(i) = 2.8 μM), mono-N-demethylation (K(i) = 1.4 μM) and di-N-demethylation (K(i) = 1.1 μM) via a competitive mechanism at therapeutic antidepressant concentrations. Imipramine moderately diminished the rate of chlorpromazine 5-sulfoxidation (K(i) = 8.7 μM, competitive inhibition), mono-N-demethylation (K(i) = 16.0 μM, non-competitive inhibition) and di-N-demethylation (K(i) = 13.5 μM mixed inhibition). Considering the serious side-effects of chlorpromazine and some of its metabolites, metabolic interactions between this neuroleptic and antidepressant drugs (especially the chlorpromazine-fluvoxamine interaction) may be of pharmacological and clinical importance. 相似文献
33.
Higuchi H Sato K Yoshida K Takahashi H Kamata M Otani K Yamaguchi N 《Psychiatry and clinical neurosciences》2008,62(3):301-306
Aims: Fluvoxamine, a selective serotonin reuptake inhibitor, is widely used to treat major depression. However, the symptomatological predictors of the response to fluvoxamine have not been studied.
Methods: This study included 100 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery and Åsberg Depression Rating Scale (MADRS) was 21 or higher. Eighty-one patients were included. Patients with a pretreatment MADRS score of ≥31 were defined as 'severe' ( n = 32) and the rest were defined as 'non-severe' ( n = 49). The three-factor model of MADRS was used for analysis: the first factor was defined by three items, the second factor was defined by four items, and the third factor was defined by three items representing dysphoria, retardation, and vegetative symptoms, respectively. Fluvoxamine (100–200 mg/day) was administered twice daily for 6 weeks.
Results: In the non-severe patients, the mean factor 3 score of the non-responders at pretreatment was significantly higher than that of the responders. However, a significant difference was observed in the mean factor 3 scores from 1 week onwards between the non-severe responders and non-responders. Furthermore, the fluvoxamine response rate in the severe patients was 75% and higher than that of the non-severe patients (65.3%).
Conclusions: This study suggested that a low factor 3 score at pretreatment was a good predictor of the response to fluvoxamine in non-severe patients. The marked efficacy of fluvoxamine in the treatment of severe patients was also confirmed. 相似文献
Methods: This study included 100 Japanese patients who fulfilled the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for the diagnosis of major depressive disorders and whose score on the Montgomery and Åsberg Depression Rating Scale (MADRS) was 21 or higher. Eighty-one patients were included. Patients with a pretreatment MADRS score of ≥31 were defined as 'severe' ( n = 32) and the rest were defined as 'non-severe' ( n = 49). The three-factor model of MADRS was used for analysis: the first factor was defined by three items, the second factor was defined by four items, and the third factor was defined by three items representing dysphoria, retardation, and vegetative symptoms, respectively. Fluvoxamine (100–200 mg/day) was administered twice daily for 6 weeks.
Results: In the non-severe patients, the mean factor 3 score of the non-responders at pretreatment was significantly higher than that of the responders. However, a significant difference was observed in the mean factor 3 scores from 1 week onwards between the non-severe responders and non-responders. Furthermore, the fluvoxamine response rate in the severe patients was 75% and higher than that of the non-severe patients (65.3%).
Conclusions: This study suggested that a low factor 3 score at pretreatment was a good predictor of the response to fluvoxamine in non-severe patients. The marked efficacy of fluvoxamine in the treatment of severe patients was also confirmed. 相似文献
34.
Different effects of fluvoxamine on rabeprazole pharmacokinetics in relation to CYP2C19 genotype status 总被引:3,自引:0,他引:3
Uno T Shimizu M Yasui-Furukori N Sugawara K Tateishi T 《British journal of clinical pharmacology》2006,61(3):309-314
AIMS: Rabeprazole is known to be a substrate of CYP2C19. Our objective was to evaluate the possible effect of an inhibitor of CYP2C19, fluvoxamine, and compare the inhibitory effect of fluvoxamine on the metabolism of rabeprazole between CYP2C19 genotypes. METHODS: A two-way randomized double-blind, placebo-controlled crossover study was performed. Twenty-one volunteers, of whom seven were homozygous extensive metabolizers (EMs), eight were heterozygous EMs and six were poor metabolizers (PMs) for CYP2C19, received two 6-day courses of either fluvoxamine 50 mg or placebo daily in a randomized fashion with a single oral dose of rabeprazole 20 mg on day 6 in all cases. Plasma concentrations of rabeprazole and its metabolite rabeprazole thioether were monitored up to 24 h after dosing. RESULTS: During placebo administration, the mean AUCs(0,infinity) of rabeprazole in homozygous EMs, heterozygous EMs and PMs were 882 (95% CI, 602, 1162) ng ml-1h , 1214 (975, 1453) ng ml-1 h and 2762 (2482, 3042) ng ml-1 h (P<0.001), respectively. Fluvoxamine treatment increased AUC(0,infinity) of rabeprazole and rabeprazole thioether by 2.8-fold (P<0.001) and 5.1-fold (P<0.01) in homozygous EMs, and by 1.7-fold (P<0.01) and 2.6-fold (P<0.01) in heterozygous EMs, and significantly prolonged the elimination half-life of rabeprazole and rabeprazole thioether in homozygous EMs and in heterozygous EMs, whereas no difference in any pharmacokinetic parameters was found in PMs. There was a significant difference in fluvoxamine-mediated percentage increase in AUC(0,infinity) of rabeprazole and rabeprazole thioether between CYP2C19 genotypes. CONCLUSIONS: The present study indicates that there are significant drug interactions between rabeprazole and fluvoxamine in EMs of CYP2C19. It is predominantly involved in rabeprazole and rabeprazole thioether metabolism in EMs. Therefore, CYP2C19 is the key determinant of rabeprazole disposition in EMs. 相似文献
35.
Differential effects of fluvoxamine, paroxetine and milnacipran for depression, especially with regard to age 总被引:3,自引:0,他引:3
INTRODUCTION: Selective serotonin reuptake inhibitors (SSRIs) and dual serotonin and noradrenaline reuptake inhibitors (SNRIs) are the most commonly prescribed classes of antidepressants, yet it is not known whether one is superior to the other. It seems that an investigation of the characteristics of patients being treated with SSRIs and SNRIs would be useful in determining which patients would be most likely to benefit from these antidepressant medications. AIMS: The purpose of this retrospective study was to compare the response to fluvoxamine, paroxetine and milnacipran treatment for depression with regard to patient age. METHODS: A retrospective cohort analysis was carried out among depression outpatients treated in the Department of Psychiatry, Kawasaki Medical School Hospital, Kurashiki, Japan, in 2001. A total of 159 patients who met the criteria and who were receiving fluvoxamine, paroxetine and milnacipran were identified. To examine the influence of antidepressants with regard to patient age, the response rate of patients aged 50 years or older was compared with that of those aged 49 years or younger. RESULTS: In patients aged 49 years or younger, the clinical effect of fluvoxamine was greater than that of the other antidepressants. Conversely, in those aged 50 years or older, milnacipran had a tendency to be more effective than the others. CONCLUSIONS: The differential response of SSRIs and SNRIs with regard to age should help to guide clinicians in determining the selection of antidepressants for depression. 相似文献
36.
Irons J 《Neuropsychiatric Disease and Treatment》2005,1(4):289-299
Fluvoxamine is a selective-serotonin reuptake inhibitor (SSRI) that has proved effective in large double-blind, randomized, controlled trials involving patients with social anxiety disorder (SAD), obsessive-compulsive disorder (OCD), and panic disorder. Improvements have also been demonstrated in patients with post-traumatic stress disorder, as well as those with a range of obsessive-compulsive spectrum disorders including binge eating disorder, bulimia nervosa, pathological gambling, and body dysmorphic disorder. Several well controlled studies have confirmed the efficacy of fluvoxamine in children and adolescents with OCD, SAD, and other anxiety disorders, and it was the first SSRI to be registered for the treatment of OCD in children. Fluvoxamine is well tolerated. In common with other SSRIs, the most frequently reported adverse event is nausea. Fluvoxamine does not cause sedation or cognitive impairment and is associated with a low risk of sexual dysfunction, suicidality, and withdrawal reactions. It is safe in overdose and has no significant effect on body weight or cardiovascular parameters. 相似文献
37.
1-氯-4-甲氧基丁烷与对三氟甲基苄腈经格氏反应得到5-甲氧基-1-(4-三氟甲基苯基)戊酮,与盐酸羟胺成肟后经与2-氯乙胺盐酸盐缩合及成盐反应制得抗抑郁药马来酸氟伏沙明,总收率40%(以对三氟甲基苄腈计). 相似文献
38.
39.
HENRY SILVER IGOR BARASH NATALIE SHMUGLIAKOV NATAN ODNOPOZOV 《Human psychopharmacology》1997,12(1):21-25
Overnight melatonin levels were measured in five male schizophrenic patients on steady antipsychotic treatment following the addition of fluvoxamine. Melatonin secretion increased in the first week of treatment and progressively decreased after 3 weeks. The findings are consistent with the development of tolerance in the processes underlying melatonin secretion. © 1997 John Wiley & Sons, Ltd. 相似文献
40.
Wen Wen Chen Chen Jiake Tang Chunyi Wang Mengyun Zhou Yongran Cheng Xiang Zhou Qi Wu Xingwei Zhang Zhanhui Feng Mingwei Wang Qin Mao 《Annals of medicine》2022,54(1):516
BackgroundThe coronavirus disease (COVID-19) epidemic has not been completely controlled. Although great achievements have been made in COVID-19 research and many antiviral drugs have shown good therapeutic effects against COVID-19, a simple oral antiviral drug for COVID-19 has not yet been developed. We conducted a meta-analysis to investigate the improvement in mortality or hospitalization rates and adverse events among COVID-19 patients with three new oral antivirals (including molnupiravir, fluvoxamine and Paxlovid).MethodsWe searched scientific and medical databases, such as PubMed, Web of Science, Embase and Cochrane Library for relevant articles and screened the references of retrieved studies on COVID-19.ResultsA total of eight studies were included in this study. The drug group included 2440 COVID-19 patients, including 54 patients who died or were hospitalized. The control group included a total of 2348 COVID-19 patients, including 118 patients who died or were hospitalized. The overall odds ratio (OR) of mortality or hospitalization was 0.33 (95% confidence interval [CI], 0.22–0.49) for COVID-19 patients in the drug group and placebo group, indicating that oral antiviral drugs were effective for COVID-19 patients and reduced the mortality or hospitalization by approximately 67%.ConclusionsThis study showed that three novel oral antivirals (molnupiravir, fluvoxamine and Paxlovid) are effective in reducing the mortality and hospitalization rates in patients with COVID-19. In addition, the three oral drugs did not increase the occurrence of adverse events, thus exhibiting good overall safety. These three oral antiviral drugs are still being studied, and the available data suggest that they will bring new hope for COVID-19 recovery and have the potential to be a breakthrough and very promising treatment for COVID-19.
KEY MESSAGES
- Many antiviral drugs have shown good therapeutic effects, and there is no simple oral antiviral drug for COVID-19 patients.
- Meta-analysis was conducted for three new oral antivirals to evaluate the improvement in mortality or hospitalization rates and adverse events among COVID-19 patients.
- We focussed on three new oral Coronavirus agents (molnupiravir, fluvoxamine and Paxlovid) and hope to provide guidance for the roll-out of oral antivirals.