Modulation of the suppressive effect of corticosterone on adult rat hippocampal cell proliferation by paroxetine

Objective The literature has shown that cognitive and emotional changes may occur after chronic treatment with glucocorticoids. This might be caused by the suppressive effect of glucocorticoids on hippocampal neurogenesis and cell proliferation. Paroxetine, a selective serotonin reuptake transporter, is a commonly used antidepressant for alleviation of signs and symptoms of clinical depression. It was discovered to promote hippocampal neurogenesis in the past few years and we wanted to investigate its interaction with glucocorticoid in this study. Methods Adult rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine for 14 d. Cell proliferation in the dentate gyrus was quantified using 5-bromo-2-deoxyuridine （BrdU） immunohistochemistry. Results The corticosterone treatment suppressed while paroxetine treatment increased hippocampal cell proliferation. More importantly, paroxetine treatment could reverse the suppressive effect of corticosterone on hippocampal cell proliferation. Conclusion This may have clinic application in preventing hippocampal damage after glucocorticoid treatment.

Comparison of paroxetine and dapoxetine, a novel selective serotonin reuptake inhibitor in the treatment of premature ejaculation

Dapoxetine hydrochloride is a selective serotonin reuptake inhibitor and the first drug approved for the on-demand treatment of premature ejaculation （PE）, Our objective in this study was to characterize the efficacy of on-demand dapoxetine （30 and 60 mg） and daily paroxetine （20 mg） usage in treating PE, We conducted a 1 month study involving a total of 150 patients. Patients were divided into three groups of 50, Group 1 were treated with on-demand dapoxetine （30 mg）, Group 2 with on-demand dapoxetine （60 mg） and Group 3 with daily paroxetine （20 rag）, Our outcome measurement was increased from baseline intravaginal ejaculatory latency time （IELT） after treatment, The IELT increased from baseline to posttreatment by 117%, 117% and 170% in the paroxetine group （P 〈 0,01）, 30 mg dapoxetine group （P 〈 0,01） and 60 mg dapoxetine group （P 〈 0.01）, respectively, The increase from baseline IELT were similar for the 30 mg dapoxetine and paroxetine groups （P 〉 0,05）, while the 60 mg dapoxetine group had a larger posttreatment IELT increase compared with the 30 mg dapoxetine （P〈 0.05） and paroxetine （P〈 0.01） groups, Dapoxetine （60 mg） 1-3 h before planned intercourse is a very effective treatment modality for PE. However, an on-demand dose of 30 mg dapoxetine is no more effective than the currently prescribed paroxetine treatment.

Improvement in quality of life in depressed patients following verum acupuncture or electroacupuncture plus paroxetine:A randomized controlled study of 157 cases

Depressed patients with scores of 17 or more on the 17 items of the Hamilton Depression Rating Scale were treated with the antidepressant drug paroxetine. They also underwent verum acupuncture or electroacupuncture at Baihui （GV20） and Yintang （GV29）. The World Health Organization Quality of Life Scale Brief Version showed a significant increase in the total scores of patients who underwent verum acupuncture and electroacupuncture for 6 weeks compared with those who were given paroxetine only; significantly increased physical domain and social relationship scores in verum acupuncture patients compared with paroxetine only; and significantly elevated psychological domain scores with electroacupuncture compared with paroxetine only. These results indicate that both verum acupuncture and electroacupuncture can improve quality of life in depressed patients undergoing paroxetine treatment,

Paroxetine engenders analgesic effects through inhibition of p38 phosphorylation in a rat migraine model

In this study, a model of migraine was established by electrical stimulation of the superior sagittal sinus in rats. These rats were then treated orally with paroxetine at doses of 2.5, 5, or 10 mg/kg per day for 14 days. Following treatment, mechanical withdrawal thresholds were significantly higher, extracellular concentrations of 5-hydroxytryptamine in the periaqueductal grey matter and nucleus reticularis gigantocellularis were higher, and the expression of phosphorylated p38 in the trigeminal nucleus caudalis was lower. Our experimental findings suggest that paroxetine has analgesic effects in a rat migraine model, which are mediated by inhibition of p38 phosphorylation.

Paroxetine vs pregabalin for the management of neuropathic pain in multiple sclerosis

AIM: To compare the effectiveness and tolerability of paroxetine vs pregabalin for the management of multiple sclerosis(MS)-induced neuropathic pain(NPP).METHODS: A randomized, flexible-dose open-label 8-wk study involving 21 relapsing-remitting MS patients with MS-induced NPP was conducted to evaluate the effectiveness and tolerability of pregabalin versus paroxetine for pain management. The trial included a 3-wk dose titration phase followed by a 5-wk stable dose phase. Primary outcome measures included daily patient-reported pain intensity as measured using a 100 mm visual analogue scale(VAS pain) and daily impact of pain on daily activities(VAS impact). Hierarchical regression modeling was conducted on each outcome to determine if within person VAS trajectory for pain and impact differed across study groups, during 56 d follow-up. RESULTS: Attrition rates were significantly greater(P < 0.001) in the paroxetine versus pregabalin study group(70% vs 18.2%, respectively). Average study duration between study groups also significantly differed(P < 0.001). Paroxetine participants completed an average of 27.3 d of treatment vs 49.5 d in the pregabalin group, with the majority of patients withdrawing due to adverse events. Due to the high attrition rates in the paroxetine study arm, the investigators stopped the study prior to achieving complete recruitment. As such, no significant differences between pregabalin and paroxetine study arms were noted for the primary outcome measures(VAS pain, VAS impact). Comparative assessment of baseline patient characteristics also revealed no significant differences between the study arms. CONCLUSION: High attrition rates associated with paroxetine use suggest that it be used with caution for MS-induced NPP. Efficacy outcomes could not be assessed due to attrition.

The Effect of Paroxetine on Depressive Symptom with Somatic Disease and Change of Platelet 5-HT Concentration

To study the effect of paroxetine on depressive symptom accompanying somatic disease and the value of platelet 5-HT concentration in the diagnosis of depression, 30 patients with depressive symptom were treated with paroxetine. All patients were evaluated on Zung and HAMD scale and assayed of platelet 5-HT concentration before and after treatment. It was found that patients had a lower level of platelet 5-HT concentration than healthy people (P<0.01). After six weeks of treatment, depressive and somatic symptoms were both improved (P<0.01) and platelet 5-HT concentration was even lower (P>0.05). It was suggested that paroxetine was a good antidepressant and platelet 5-HT concentration was useful in the screening of depression.

Administration of Zinc with Paroxetine Improved the Forced Swim Test Behavioral Pattern of Treated Mice in Acute and Sub-Acute Study

Despite progressive improvement in treating major depressive disorder (MDD), it remains mostly unresponsive to one antidepressant medication. Zinc is a brain highly abundant trace metal, a brain derived neurotrophic factor (BDNF) inducer, a modulator of synaptic plasticity and potent suppressor of the NMDA receptors. We proposed that co-administration of zinc with the antide-pressants may represent a valuable regimen to improve the efficacy of these drugs. This work has been implemented to evaluate the behavioral changes of acute and sub-acute co-administration of zinc with Paroxtine in mice. Methods: The animals were injected intra-peritoneal with either Paroxtine (20 mg/kg) which was a selective serotonin reuptake inhibitor (SSRI), zinc sulfate (30 mg/kg) or Paroxtine in combination with zinc for one day and one week (once daily). The pattern of the animal behavior was assessed in the forced swim test (FST). Results and Discussion: The behavioral patterns of the animals in the FST include immobility, swimming and climbing. Successful antidepressant should decrease the immobility time with either increase in swimming and/or climbing behavior based on the drug pharmacological activity. Our results revealed a significant decrease of immobility and increase of swimming behavior indicating serotonin-dependent pharmacological activity of Paroxtine or zinc alone as well as in the animals treated with zinc in combination with Paroxtine. There was no significant difference in the animals’ behavior between acute and sub-acute treatment with zinc or even upon its addition to paroxetine. Our data support the concept that co-administration of zinc may provide further antidepressant activity. Zinc may offer additional clinical value particularly in geriatric patients or other populations where zinc level has shown dramatic decrease.

Influence of paroxetine and cognitive/behavioral strategies in neurocardiogenic syncope and depression: a case report

OBJECTIVE: Neurocardiogenic syncope (NCS) is a condition where the patient has a temporary loss of consciousness or feelings of weakness and fatigue. There are triggers such as prolonged sitting or standing, pain, and heavy exercise, but often episodes are random. Treatments are limited and the use of specific serotonin reuptake inhibitors (SSRI) have had mixed results, but a limited number of studies have suggested that paroxetine may be effective in improving the symptoms of NCS. METHODS: This is a single case report of a 20-year old female who was diagnosed with NCS by a tilt test and treated conservatively with increased fluid and salt intake, and counter-pressure maneuvers. She was given one dose of sertraline, but immediately experienced disturbing visual images. She presented at the Depression Center with moderate depressive symptoms and was started on paroxetine and given cognitive/behavioral strategies to manage the NCS. RESULTS: Since the patient had a negative experience with a prior SSRI, she was started on a low dose of paroxetine and omega-3 fatty acids. She also was given a detailed explanation of NCS and a number of cognitive/behavioral strategies such as deep breathing, progressive relaxation, imagery, and sleep. CONCLUSION: After 2-weeks of the multi-faceted treatment approach, she had a significant decrease in her depressive symptoms. After 6-months, the patient had no episodes of syncope and no depressive symptoms. She was able to stand for long periods and exercise without feelings of weakness and fatigue. A multimodal approach may offer the best treatment strategy to achieve full remission in patients with NCS.

Rate of social anxiety disorder, its comorbidity with depression and paroxetine effects in outpatients in Japan

The prevalence of persons with social anxiety disorder (SAD) in Japan remains unknown. This study examined 293 patients with age between 20 and 60 at first visit on the outpatient clinic of psychiatry by the section of social phobia of M.I.N.I. and DSM-IV. After that, 10 patients with both SAD out of 16 patients (trial recruited) completed 12 weeks of treatment with paroxetine. Among 63 patients with 4 points and 40 patients with 3 points on the M.I.N.I., 21 patients (33%) and 16 patients (40%) were diagnosed as SAD on DSM-IV criteria, respectively. Together, 37 patients (12.6%) were diagnosed as SAD out of the 293 outpatients. Among 37 patients with SAD, 23 patients (62%) had comorbid depression. As for 10 patients after treatment with paroxetine, 8 patients improved from the point of recovery of depression (HAM-D scores below 10), whereas only 4 patients improved from the point of recovery of social phobia (L-SAS scores below 30). Three points as well as 4 points on the M.I.N.I. is meaningful for the diagnosis of SAD. For a while, paroxetine exerted less beneficial effects on SAD rather than on depression.

Paroxetine Augments while Naloxone Abolishes the Analgesic Effect of Paracetamol in Acute Nociceptive Pain in Mice

The mechanism(s) of analgesic action of paracetamol (acetaminophen;N-acetyl-p-aminophenol) remains controversial. Previous studies on rats suggested that the antinociceptive action of paracetamol might involve the central descending inhibitory pain pathways recruiting both a serotoninergic and an opioidergic system. This study explores this issue in mice using paroxetine, the most potent selective serotonin re-uptake inhibitor, and the nonselective opioid pure antagonist naloxone. Animals were divided into two main groups for two separate experiments, each subdivided into 3 subgroups. In both experiments;the first group served as control, the second group received paracetamol (200 mg/kg, i.p). In one experiment, the third group received paroxetine (20 mg/kg p.o for 7 days) before paracetamol. In the other experiment, animals of the third group were pretreated with naloxone (5 mg/kg, i.p) 30 min before paracetamol. The antinociceptive effect of paracetamol was tested using the hot plate test. Paracetamol displayed a significant antinociceptive activity that was augmented by pretreatment with paroxetine as was shown by maintenance of its effect beyond that shown by paracetamol alone. On the other hand, pretreatment with naloxone abolished paracetamol’s antinociceptive activity in the hot-plate test. These results extended the previous observation in rats that the antinociceptive effect of paracetamol involved activation of a central descending pain inhibitory pathway with serotonin and opioidergic peptides being potential mediators recruited.

护理干预及联合帕罗西汀对癌症抑郁焦虑患者生活质量的影响

目的探讨护理干预及联合帕罗西汀(Paroxetine)对癌症抑郁焦虑患者生活质量的影响。方法将90例癌症抑郁患者随机分为对照组、护理干预组、护理干预联合帕罗西汀组,每组30例。对照组:在治疗癌症的基础上,给予传统护理。护理干预组:给予护理干预和安慰剂1片/d。护理干预联合帕罗西汀组:在护理干预的同时予帕罗西汀20mg/d,各组分别于治疗第6周末进行评价。结果治疗后护理干预组及护理干预联合帕罗西汀组HAMD、HAMA总分均明显下降(P<0.01);并低于对照组(P<0.01);护理干预联合帕罗西汀组又明显低于护理干预组(P<0.05)。护理干预组临床有效率明显高于对照组(P<0.01),护理干预联合帕罗西汀组又明显高于护理干预组(P<0.05)。护理干预组生活质量的改善的有效率明显高于对照组(P<0.01);护理干预联合帕罗西汀组又明显高于护理干预组(P<0.05)。结论护理干预是以人为中心,从人的整体出发,从社会心理、疾病等几个方面进行护理,可明显改善癌症患者抑郁、焦虑的生活质量,有选择性的应用帕罗西汀等抗抑郁药物可进一步提高护理干预的作用。

按需服用Tramadol与日服Paroxetine哪一个更适合终身服用治疗早泄呢?

早泄是最常见的男性性功能障碍之一。目前临床上具有多种治疗方法，但临床效果极富争议。Paroxetine和tramadolHCl是目前治疗该病比较有效的药物。本文献就这两种药物（每日服用Paroxetine还是按需服用tramadolHCl的疗效做比较，以看哪一种更适合作为一种终身治疗早泄药物。以IELT（阴道内射精时间）和AIPE（早泄指数）来评估药物疗效。研究对象是取Mansoura大学医院在2008年4月至2009年3月参加男性学协会的患有早泄的患者。患者均经过严格筛选，需满足8项标准（参照文献）才能纳入研究。最后35例患者纳入研究。其中17例患者使用tramadolHCl，采用按需给药，临床观察前2-3h使用药物50mg；另外18例患者使用Paroxetine，采用每日给药，每日早餐后使用药物20mg。治疗周期为两个阶段，每个阶段六周，两个阶段治疗药物相同。

赛乐特治疗考前焦虑对成绩的影响研究

目的探索精神类药物(赛乐特,Paroxetine Hydrochloride Tablets,简称PHT)治疗考前焦虑后是否有利于个体正常能力的发挥。方法以高三学生为被试,观察赛乐特治疗考前焦虑后对他们名次提高的影响。结果被试考前焦虑的解除反而导致成绩和名次的明显下降。结论用赛乐特治疗考前焦虑其实不利于个体正常能力的发挥,适量的考前焦虑或许更有利于个体正常能力的发挥。

Paroxetine ameliorates prodromal emotional dysfunction and late-onset memory deficit in Alzheimer’s disease mice

Background Neuropsychiatric symptoms(NPS)such as depression,anxiety,apathy,and irritability occur in prodromal phases of clinical Alzheimer’s disease(AD),which might be an increased risk for later developing AD.Here we treated young APP/PS1 AD model mice prophylactically with serotonin-selective re-uptake inhibitor(SSRI)paroxetine and investigated the protective role of anti-depressant agent in emotional abnormalities and cognitive defects during disease progress.Methods To investigate the protective role of paroxetine in emotional abnormalities and cognitive defects during disease progress,we performed emotional behaviors of 3 months old APP/PS1 mouse following oral administration of paroxetine prophylactically starting at 1 month of age.Next,we tested the cognitive,biochemical and pathological,effects of long term administration of paroxetine at 6 months old.Results Our results showed that AD mice displayed emotional dysfunction in the early stage.Prophylactic administration of paroxetine ameliorated the initial emotional abnormalities and preserved the eventual memory function in AD mice.Conclusion Our data indicate that prophylactic administration of paroxetine ameliorates the emotional dysfunction and memory deficit in AD mice.These neuroprotective effects are attributable to functional restoration of glutamate receptor(GluN2A)in AD mice.

Clinical Observation on Treatment of Depression by Electro-Acupuncture Combined with Paroxetine

Objective： To observe the clinical efficacy and adverse reactions of Paroxetine combined with electro-acupuncture （EA） in treating depression. Methods： Forty-two patients with depression were randomly assigned to the observation group （22 patients） treated with EA combined with Paroxetine, and the control group （20 patients） treated with Paroxetine alone, and the therapeutic course for both groups was 6 weeks. The therapeutic efficacy and adverse reactions were evaluated with scores by Hamilton depression scale （HAMD） and treatment emergent symptoms scale （TESS）, respectively. Results： HAMD scores determined at the end of the 1st, 2nd, 4th, and 6th week of the treatment course were significantly lower in the observation group than those in the control group （P〈0.05）. The significant improvement rate evaluated at the end of the 6-week treatment was remarkably higher in the observation group than that in the control group （72.7% vs 40.0%）. No significant difference of TESS scores was found between the two groups. Conclusion： EA combined with Paroxetine has better clinical efficacy than that of Paroxetine alone, with milder adverse reaction and quicker initiation of effect.

Roles of paroxetine and corticosterone on adult mammalian ciliary body cell proliferation

Background The neurogenesis in retina of adult mammals is generally abolished, and this renders the retina lack of regenerative capacity. Despite this, there is a small population of nestin-positive cells in the ciliary epithelium which retains neurogenic potential. The present study aimed at investigating the effect of two drugs, corticosterone and paroxetine, on the cell proliferation of the ciliary body. Methods Adult Sprague-Dawley rats were given vehicle, corticosterone, paroxetine, or both corticosterone and paroxetine treatment for 14 days. Cell proliferation in the ciliary body was quantified using 5-bromo-2-deoxyuridine （BrdU） immunohistochemistry. Co-labelling of BrdU and stem cell marker was used to phenotype the BrdU immunoreactive cells. Results Corticosterone treatment suppressed while paroxetine treatment increased the cell proliferation of the ciliary body. Co-labelling with cell markers revealed that the BrdU positive cells also showed nestin expression but not glial fJbrillary acidic protein （GFAP）. Conclusions The results illustrate that proliferation of retinal progenitor cells situated in ciliary body are subjected to regulation by selective serotonin reuptake Jnhibitors （SSRI） and corticosteroJd, which is similar to our previous findings in neurogenic regions in central nervous system （CNS）. Paroxetine treatment could reverse the suppressive effect of corticosterone on ciliary body cell proliferation. This provides information for future investigation of retinal stem cell biology and potential treatment of retinal degenerative diseases.

基于G-蛋白偶联受体激酶2抑制剂治疗心力衰竭的合理药物设计（英文）

G protein-coupled receptors(GPCRs)convert extracellular stimuli in the form of hormones,odorants and light into profound changes in cell homeostasis.Their timely desensitization is critical for cells to rapidly respond to changes in their environment and to avoid damage from sustained signaling.Seven GPCR kinases(GRKs)phosphorylate and regulate the activity of most of the^800 GPCRs in the human genome.Although GRKs normally play an adaptive role,in conditions such as chronic heart failure they are overexpressed and linked to disease progression.GRK2 and GRK5 have thus become important targets for the treatment of heart failure and pathological cardiac hypertrophy,respectively.Our lab has determined atomic structures representing all three vertebrate GRK subfamilies,and is now in the midst of a campaign to develop selective inhibitors of these enzymes using structure-based rational design.We have identified the FDA approved drug paroxetine as a selective GRK2 inhibitor,determined the crystal structure of the GRK2·paroxetine complex and,in collaboration with the Koch lab,showed that the drug improves contractility in myocytes and,most impressively,recovery in postmyocardial infarcted mice.Since then,we have identified additional chemical scaffolds that exhibit even higher potency and/or selectivity for GRK5.Using a"hybrid"inhibitor design approach we have generated GRK selective chemical probes that exhibit improved potency and stability and are able to increase inotropy and dampen the hypertrophic response in cardiomyocytes and small animal models.Structural analysis has revealed the molecular basis for selectivity and potency in many of these compounds,allowing for the design of future generations of GRK chemical probes.

Noven Pharmaceuticals公司报告关于low—dose paroxetine mesilatel的Ⅲ期临床数据

Noven Pharmaceuticals公司报告了2项拟定的Ⅲ期临床研究的第1项研究（NCT01101841）的主要结果。