Prenatal exposure to the fluoride containing psychiatric drug fluoxetine and anti-oxidative alterations in the neonatal rat brain

Fluoride is a key ingredient of many psychiatric drugs like fluoxetine (Prozac^®, Fluoxetine^®). Pregnant women frequently use this drug as they suffer from depression and anxiety disorders during this period. Fluoxetine is able to reach the fetus through the placenta and passes to the newborn through milk. In the present study, female Wistar rats were treated with 5, 10, and 20 mg/L fluoxetine (containing 94% fluorides) from pregnancy day 10 to day 20. After delivery, the levels of the enzymatic antioxidants in the brain of their offspring at postnatal day 2 were measured. The results showed that, in all fluoxetine exposed groups compared with the control group, there was a significant decrease (P < 0.01) in the glutathione, catalase, glutathione S-transferases and potassium and a non- significant increase (P > 0.05) in the activity of malondialdehyde and creatine kinase. The results suggest that fluoxetine may be a developmental neurotoxicant due to presence of fluoride hence must be used carefully during pregnancy.     

Aggregation and Phase Separation Phenomenon of Amitriptyline Hydrochloride Under the Influence of Pharmaceutical Excipients

The interaction between the amphiphilic drug amitriptyline hydrochloride (AMT) and the nonionic surfactants used in drug delivery has been investigated. Herein, we report the micellization behavior of AMT in presence of ethoxylated alkyl phenols in aqueous medium and the clouding phenomenon in the absence and presence of different nonionic surfactants in buffer solution. The values of critical micelle concentration (CMC) of AMT obtained using the conductivity method, decrease as nonionic surfactant concentration increases. With an increase in temperature, the CMC first increases and then decreases. At 303.15 K, the maximum CMC values were obtained with or without nonionic surfactant. The results obtained indicate attractive interactions (synergism) between the two mixing amphiphiles in solution. The experimentally obtained critical micelle concentration (CMC) values are always lower than ideal CMC values. Micellar mole fraction (X₁) values, calculated by different proposed models, show the contribution of nonionic surfactant concentration. At a fixed drug concentration (50 mmol kg^?1) and pH (=6.7) nonionic surfactants show continuous increase in cloud point (CP). Increase in drug concentration and pH, in the presence of fixed amounts of nonionic surfactant, increases and decreases the CP, respectively.     

抑郁症发病机制与临床抗抑郁药研究进展

抑郁症是一种常见的精神类疾病,但目前其确切的病因病理机制尚不清楚。神经递质失衡、免疫功能紊乱、神经内分泌失调、神经可塑性异常改变以及遗传因素影响等均与抑郁症发病密切相关。尽管抗抑郁药的研究取得了一定程度的发展,但是目前的药物大多作用靶点单一,起效慢,不良反应多,临床疗效不甚理想。多靶点,多系统共同作用类抗抑郁药物的研发已成为新药发展的主要研究方向。本文就抑郁症的神经生化机制及抗抑郁药的作用特点作一综述,为临床抗抑郁药的选择及开发研究新药提供借鉴。     

利培酮联合抗抑郁药物治疗抑郁症对照研究的 Meta 分析

目的: 评价利培酮联合抗抑郁药物与抗抑郁药物单一治疗抑郁症的有效性与安全性的差异。方法: 应用循证医学方法对符合标准的10项研究进行分析,评价利培酮联合抗抑郁药物与抗抑郁药物单一治疗抑郁症的疗效、效应大小、痊愈率以及副作用的差异。结果: 同质性检验:(1)有效性:χ²=7.26,d_f=9(P>0.05);(2)安全性:χ²=3.41,d_f=2(P>0.05)。综合检验:研究组与对照组在第1、2、4、6、8周末的综合检验分别为Z₁=14.19(P<0.01)、Z₂=14.00(P<0.01)、Z₄=17.40(P<0.01)、Z₆=12.10(P<0.01)、Z₈=5.94(P<0.01)。效应大小:无论是研究组还是对照组,在第1、2、4、6、8周末与治疗前进行比较的治疗效应大多数达到0.5以上;研究组与对照组干预处理效应的差异效应在不同时段的差异效应都大于0.8。有效性比较:应用固定效应模型或随机效应模型显示研究组所有时段痊愈率、显效率均非常显著高于对照组,而无效率低于对照组(8周末除外)。副作用:两组之间的副作用差异没有显著性(Z=0.20~1.15,P>0.05)。结论: 小剂量利培酮联合抗抑郁药物治疗抑郁症是一种良好的方法,可能特别适宜于难治性抑郁症。