一种杂环类抗抑郁新药venlafaxine

传统的三环类抗抑郁药（TCA）和单胺氧化酶抑制剂（MAOI）常引起许多不良反应，如镇静、失眠、体位性低血压、尿潴留、恶心、呕吐及与食物的相互作用。理想的新型抗抑郁药疗效应与当前使用的药物相当，且无因不良反应而导致的不顺从用药问题。venlafaxine在抗抑郁作用方面与TCA，MAOI，选择性5－HT重摄取抑制剂相当，但其抗胆碱能、肾上腺素能和组胺能的不良反应轻微，因此美国食品和药品管理局（FDA）已正式批准投放市场。本文对venlafaxine的药理学、药效学、药动学、临床应用研究及其安全性和不良反应进行了介绍。

新型抗抑郁药Venlafaxine

本文通过分析现今各种抗抑郁药的异同，并经由临床前及临床药理学研究报告之总结，介绍一种起效快、耐受性好、同时对５－ＨＴ和ＮＥ回收都有较强抑制作用新药Ｖｅｎｌａｆａｘｉｎｅ。

Tunable and sustained-release characteristics of venlafaxine hydrochloride from chitosan–carbomer matrix tablets based on in situ formed polyelectrolyte complex film coating

The objective of this study is to design sustained-release tablets using matrix technology, which can well control the release of highly water-soluble drugs with good system robustness and simple preparation process. Taking venlafaxine hydrochloride(VH) as a drug model, the feasibility of using chitosan(CS), carbomer(CBM) combination system to achieve this goal was studied. Formulation and process variables influencing drug release from CS–CBM matrix tablets were investigated. It was found that CS–CBM combination system weakened the potential influence of CS, CBM material properties and gastric emptying time on drug release profile. Demonstrated by direct observation, differential scanning calorimetry(DSC) and Fourier transform infrared spectroscopy(FTIR), in situ self-assembled polyelectrolyte complex(PEC) film was formed on the tablet surface during gastrointestinal tract transition, which contributed to the tunable and robust control of drug release. The sustained drug release behavior was further demonstrated in vivo in Beagle dogs, with level A in vitro and in vivo correlation(IVIVC) established successfully. In conclusion, CS–CBM matrix tablets are promising system to tune and control the release of highly water-soluble drugs with good system robustness.

Long-term follow-up of a patient with venlafaxine-induced diurnal bruxism treated with an occlusal splint:A case report

BACKGROUND Bruxism is a jaw-muscle activity characterized by the clenching or grinding of teeth. It can be divided into nocturnal bruxism and diurnal bruxism(DB). DB secondary to antidepressants is rare and refractory. Reports associated with antidepressant-induced DB are mostly anecdotal without long-term follow-up.The effect of drug intervention on antidepressant-induced DB is still contested.We herein report the first case of successful treatment of venlafaxine-induced DB with an occlusal splint.CASE SUMMARY This case report describes detailed 7-year follow-up of a patient with venlafaxineinduced DB treated with an occlusal splint. The patient who complained about involuntary daytime tooth grinding after taking venlafaxine for a period of 4 mo and was diagnosed with venlafaxine-induced DB. Subsequently, an occlusal splint with modified bilateral buccal-pterygoid pads was used to treat his tooth grinding and to protect the dental structures from tooth wearing. The patient reported remission of symptoms after several months of treatment. His grinding activity was gradually and stably controlled after 2 years, with an almost complete recovery from DB after 6 years.CONCLUSION The maxillary buccal-pterygoid splint can be used as a noninvasive approach to treat venlafaxine-induced DB.

Development and Optimization of Venlafaxine Hydrochloride Sustained Release Triple Layer Tablets Adopting Quality by Design Approach

Purpose:Venlafaxine hydrochloride sustained release formulation increases patient compliance by reducing frequency of administration and it also reduces side effects like nausea and vomiting. Hence the objective of present investigation was to develop triple layer sustained release tablets of venlafaxine HCl using xanthan gum or polyethylene oxide. Methods:The venlafaxine HCl 150 mg sustained release tablets were prepared by wet granulation technique where drug was incorporated in middle layer with part of polymer. The barrier layers were composed of remaining polymer and other excipients. The granules and tablets were characterised. Optimized batches were also tested for drug release at different pH and in presence of ethanol, for kinetics of drug release and for water uptake/swelling. Results: Preliminary trials of monolayer tablet showed burst release due to high dose and solubility of venlafaxine HCl and hence triple layer tablets were developed. Granules of middle layer exhibited good flow properties. The comparative drug release to Effexor? XR capsule 150 mg could be achieved by modulating the concentration of polymer and diluents in middle layer as well as in barrier layers. Higher amount of polyethylene oxide was required as compared to xanthan gum which may be due to high water uptake and poor gel strength of polyethylene oxide. The optimized formulations showed pH independent drug release as well as ethanol had no effect on drug release. Effexor? XR capsule and optimized batches followed Weibull kinetics for drug release. The radar diagrams showed the comparable drug release to innovator in both the optimized formulations but point to point correlation was observed in batch with xanthan gum. Conclusion: The layered matrix tablets formulated successfully using hydrophilic polymers, xanthan gum or polyethylene oxide, to sustain the release of highly soluble drug like venlafaxine HCl.

Overdose of Venlafaxine with Mild Outcome

The antidepressant venlafaxine in overdose can lead to serotonin syndrome, seizures, QTc interval prolongation and can increase the risk of cardiac arrhythmias. It has been reported to be more toxic in overdose than other new antidepressants. We report a case of venlafaxine intoxication with a venlafaxine/O-desmethylvenlafaxine serum level of 2861/2670 ng/mL 22 h after ingestion. This is one of the so far highest survived venlafaxin serum levels. In contrast to other reported survived venlafaxin overdoses with high serum levels no clinical signs of intoxication were observed in our case. So venlafaxine overdose not necessarily leads to life-threatening signs of intoxication.

Construction and properties of venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres

The aim of this work is to develop a venlafaxine hydrochloride sustained release system based on hollow mesoporous silica microspheres(HMSMs).HMSMs were innovatively prepared with tetraethyl silicate(TEOS)as the precursor and volatile n-heptane as a soft template.The obtained HMSMs show a well-defined hollow structure with an average size of 967 nm and pore volume of 0.85 cm^(3)/g,implying it is a potential drug carrier.Subsequently,venlafaxine hydrochloride(VF)was absorbed in the HMSMs with a content of 37.67% or so.The sustained release effect is further measured by the dissolution in-strument at 37℃ and 50 rpm in ultrapure water.The results showed that the HMSMs/VF system shows good sustained release properties compared with sustained release tablets with hydroxypropyl meth-ylcellulose as the main component.This HMSMs sustained release system appears to be a promising candidate for a sustained drug release.

Voltammetric determination of venlafaxine as an antidepressant drug employing Gd_2O_3 nanoparticles graphite screen printed electrode

Graphite screen printed electrode modified with Gd_2 O_3 nanoparticles(Gd_2 O_3/SPE) was developed for the determination of venlafaxine(VF). The Gd_2 O_3 nanoparticles were thoroughly characterized by scanning electron microscopy(SEM), transmission electron microscopy(TEM) and X-ray diffraction(XRD) analyses. To study the electrochemical behaviour of venlafaxine cyclic voltammetry(CV), chronoamperometry(CHA)and differential pulse voltammetry(DPV) were employed. These studies reveal that the oxidation of venlafaxine is facilitated at Gd_2 O_3/SPE. After optimization of analytical conditions, analysis of venlafaxine using the modified electrode in 0.1 mol/L PBS(pH 7.0) demonstrates that the peak currents corresponding to venlafaxine vary linearly with its concentration in the range of 5.0 ×10^(-6)-9.0 × 10^(-4) mol/L. The detection limit(S/N = 3) of 2.1 × 10^(-7) mol/L is obtained for venlafaxine using DPV. The prepared modified electrode benefits from advantages such as simple preparation method, high sensitivity and low detection limit.Moreover, the evaluation of practical applicability of this proposed method is successful in the identification of venlafaxine in pharmaceutical formulations, urine and water samples.

Association between SLC17A7 gene polymorphisms and venlafaxine for major depressive disorder in a Chinese Han population:a prospective pharmacogenetic case-control study

Objective: Venlafaxine is a common antidepressant and its therapeutic effect varies among people with different genetic backgrounds. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in theSLC17A7 gene are associated with the treatment outcome of venlafaxine in a Chinese Han population with major depressive disorder.Methods: This prospective pharmacogenetic case-control study that involved genotyping of four SNPs ofSLC17A7 was conducted on 175 major depressive disorder patients of Chinese Han origin, aged 18 to 65 years, participated in the study from April 2005 to September 2006. Comparisons of allele and genotype frequencies of all SNPs were performed between the responder/remission group and the nonresponder/nonremission group. This study was approved by the Institutional Ethics Committee of Sichuan University (approval No. 20151112-265).Results: The allele and genotype frequencies of the four candidate SNPs inSCL17A7 showed no significant difference between responders and nonresponders. Meanwhile, no significant difference was detected in the four investigatedSLC17A7 SNPs between patients who did and did not exhibit remission. Although one of the investigatedSLC17A7 variants (rs1578944) demonstrated a significant association (P=0.022) with a response to venlafaxine after 6 weeks of treatment in the survival analysis, the association was unclear after a Bonferroni multiple comparisons test was conducted.Conclusion: No significant association exists between the four candidate SNPs (rs1043558, rs1320301, rs1578944, and rs74174284) inSLC17A7 and venlafaxine treatment in the Chinese Han population.

Montmorillonite/Poly(L-Lactide)microcomposite spheres as reservoirs of antidepressant drugs and their controlled release property

This work evaluates intercalation of Nortriptyline(NT)and Venlafaxine(VFX)in an interlayer gallery of Na^(+)-MMT(Montmorillonite),which was further compounded with Poly(LLactide)(PLLA)to form microcomposite spheres(MPs)for oral controlled drug delivery.The XRD patterns,thermal and spectroscopic analyses indicated intercalation of drugs into the MMT interlayer that was stabilized by electrostatic interaction.No significant changes in structural and functional properties of drugs were found in the MMT layers.In vitro drug release studies showed controlled release pattern.

Effexor XR治疗惊恐症获美国批准

Wyeth公司的SNRI抗抑郁剂Effexor XR（exeended-release venlafaxine，文拉法辛延长释放片）（Ⅰ）已获得美国FDA的批准，用于治疗成人惊恐症这一附加适应症。