For postmenopausal women who fear hormone therapy, women 60 years of age with continuous, severe hot flushing or women with a history of breast cancer, we should consider selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs) as therapeutic agents. Base on the results from a meta-analysis and clinical trials regarding hot flushing, paroxetine and the conetrolled-release formultation of paroxetine have been shown to effectively reduce hot flushing by 30~40% and 60~70%, respectively, and 13~41% more reductions as compared to placebo. Venlafaxine reduced hot flushes by 30~60% (133% reductions compared to placebo), and desvenlafaxine reduced hot flushes by 30~70%. Fluoxetine and citalopram were shown to be less effective than paroxetine and venlafaxine, by 20% (113% reductions compared to placebo) and 40~50%, respectively. Sertraline reduced hot flushes 3~18% compared to the placebo group, but was considered ineffective. Citalopram (20 mg), paroxetine (10 mg), venlafaxine (37.5~150 mg), and desvenlafaxine (100~200 mg) not only reduced vasomotor symptoms, but demonstrated additional beneficial outcomes with respect to sleep disturbances, mood, the vigor index, and improved quality of life. Citalopram (20 mg), fluoxetine (20 mg), paroxetine (10 mg), venlafaxine (75~150 mg), and desvenlafaxine (150 mg) are recommended at the corresponding doses after weighing the risks and benefits of these medications. SSRIs and SNRIs were shown to interrupt the conversion of tamoxifen into the active metabolite, endoxifen, and thus SSRIs and SNRIs must not be used in breast cancer patients who are taking tamoxifen. Paroxetine suppressed vasomotor symptoms most potently, followed by fluoxetine, sertraline, citalopram, and venlafaxine.
Breast Neoplasms ; Citalopram ; Cyclohexanols ; Female ; Fluoxetine ; Flushing ; Humans ; Menopause ; Norepinephrine ; Paroxetine ; Quality of Life ; Risk Assessment ; Serotonin ; Serotonin Uptake Inhibitors ; Sertraline ; Tamoxifen ; Desvenlafaxine Succinate ; Venlafaxine Hydrochloride

Venlafaxine is among the most widely prescribed antidepressants. It is extensively metabolized to O-desmethylvenlafaxine via cytochrome P450 (CYP) 2D6. We report a case of acute toxic hepatitis resulting from venlafaxine in a 54-year-old woman with pain disorder. During venlafaxine treatment, laboratory tests revealed elevated liver enzymes with a maximum of 169 IU/L for aspartate transaminase (AST) and 166 IU/L for alanine transaminase (ALT). AST and ALT levels returned to normal after 6 days of discontinuation of venlafaxine. The patient was finally diagnosed with acute toxic hepatitis through liver biopsy. This case indicates the importance that clinicians should be aware of the hepatotoxicity of venlafaxine in practice.
Alanine Transaminase ; Antidepressive Agents ; Aspartate Aminotransferases ; Biopsy ; Cyclohexanols ; Cytochrome P-450 Enzyme System ; Drug Toxicity ; Drug-Induced Liver Injury ; Female ; Humans ; Liver ; Middle Aged ; Somatoform Disorders ; Desvenlafaxine Succinate ; Venlafaxine Hydrochloride

OBJECTIVETo explore the usefulness of a head-space gas chromatography in the determination of residual solvents including methanol,ethanol,ethyl ether,and petroleum ether in muscone in artificial musk.

METHODSThe head-space gas chromatography was performed on HP-5(30 m×0.53 mm,5 Μm)capillary column with a hydrogen flame ionization detector. The carrier gas was nitrogen and the solvent was dimethyl sulfoxide. The injector temperature and the detector temperature were controlled at 180 ℃ and 250 ℃,respectively. The containers of head-space injector were preheated at 80 ℃ for 15 minutes. The column temperature was programmed raised,which achieved baseline separation of the components.

RESULTSThe results showed a good linear relationship for methanol,ethanol,ethyl ether,and petroleum ether(60-90 ℃)in the range of each consistency; and the limit of detection was 0.8,1.0,0.1,and 0.3 Μg/ml,respectively. The precision and average recoveries were satisfactory.

CONCLUSIONThe head-space gas chromatography is simple,rapid,and precise technique for measuring residual solvents in muscone.

Chromatography, Gas ; Cycloparaffins ; chemistry ; Drug Contamination ; Drugs, Chinese Herbal ; chemistry ; Ethanol ; analysis ; Solvents ; analysis

This study aimed to investigate the enhancing effect of muscone on the transdermal penetration of traditional Chinese medicine ingredients and explore its possible mechanism of action. The Franz diffusion cells were employed to investigate the effect of muscone on the transdermal permeation of a series of model drugs with a wide range of log P values. The solubilities at saturation and the stratum corneum(SC)/vehicle partition coefficients of model drugs were measured to evaluate the effect of muscone on drug thermodynamic activities and partition of drugs into SC. Attenuated total reflectance-Fourier transform infrared spectroscopy(ATR-FTIR) was employed to explore the effect of muscone on the molecular structure of SC. The results showed that muscone significantly promoted the transdermal penetration of hydrophilic and lipophilic drugs, and the enhancement ratio(ER) increased with the decrease in the log P. Muscone could interact with the SC lipids to increase the disorder and fluidity of lipid bilayer packing, which improved skin permeability and promoted transdermal absorption of drugs. This study provides a scientific basis for the application of muscone in traditional Chinese medicine topical preparations.
Administration, Cutaneous ; Animals ; Cycloparaffins ; Medicine, Chinese Traditional ; Permeability ; Rats ; Rats, Sprague-Dawley ; Skin/metabolism* ; Skin Absorption

To develop an ophthalmic preparation of Shedan, an in situ forming gel was prepared with the formulation containing 18% of poloxamer 407 and 5% of poloxamer 188 by response surface designs plus central composite designs. The rheology results showed that LVE range gamma should limited within 0.5%, Shedan high-frequency region, and the thixotropy recovery time is less than 5 seconds. The phase transition temperature was 33.25 °C according to curve of storage modulus and loss modulus determined by temperature scanning. Surface tension and osmometer of it determined by surface tension meter and dew point osmometer were 36.43 mN · m(-1), and 320.6 mOsm · kg(-1), respectively. Fluorescein sodium was selected as the marker to monitor the corneal residence time, and the results showed that Shedan gel could prolong drug residence for 180 min. In line with zero-order kinetics, releases of muscone and salvianolic acid B in vitro depends on gels erosion. The results of rabbit ocular irritation experiments suggested that Shedan in situ forming gel was biocompatible and nonirritant. In conclusion, a novel Shedan in situ forming gel was developed and characterized for potential drug treatment of retinal vein occlusion.
Animals ; Benzofurans ; chemistry ; Cycloparaffins ; chemistry ; Female ; Gels ; chemistry ; Male ; Ophthalmic Solutions ; Poloxamer ; chemistry ; Rabbits ; Retinal Vein Occlusion ; drug therapy ; Viscosity

OBJECTIVETo explore the influence of borneol on intestinal absorption of muscone in rats.

METHODAn in situ intestinal circulation perfusion experiment was used to study the changes in intestinal absorption kinetics of muscone before and after being compatible with borneol.

RESULTCompared with the muscone group (MG), the absorption rate constants (Ka), the half-life period (T1/2) and the absorption rate (A) of muscone in the borneol + muscone group (BMG) were on the rise, but with no significant difference; after being compatible with borneol for a long period, Ka, T1/2 and A in the last borneol on muscone group (LBMG) increased, with significant difference (P < 0.05). in duodenum, LBMG showed better effects than MG (T1/2, P < 0.05); and so did in jejunum (Ka, P < 0.05; T1/2, P < 0.05); in ileum, there was no significant statistical difference between LBMG and MG.

CONCLUSIONBorneol can promote the intestinal absorption of muscone in rats to some extent.

Animals ; Bornanes ; pharmacology ; Cycloparaffins ; pharmacokinetics ; Drug Interactions ; Drugs, Chinese Herbal ; pharmacokinetics ; pharmacology ; Intestinal Absorption ; drug effects ; Intestines ; drug effects ; metabolism ; Male ; Rats ; Rats, Wistar

OBJECTIVETo compare the penetrating rate of muscone in different inclusion complexes and liposome.

METHODThe transdermal effect of muscone in different inclusion complexes and liposome was studied comparatively on mouse [corrected] skin with 40% EtOH as the absorption solution and with an improved Franz diffuse cell.

RESULTAmong the different inclusion complexes and liposome, the penetrating rate of muscone in the HP-beta-cyclodextrin inclusion and the liposome were higher than muscone, and that of muscone in the beta-cyclodextrin inclusion is the lowest.

CONCLUSIONThe HP-beta-cyclodextrin inclusion and the liposome can hence the muscone transdermal speed.

2-Hydroxypropyl-beta-cyclodextrin ; Animals ; Cycloparaffins ; administration & dosage ; pharmacokinetics ; Drug Carriers ; Drug Stability ; In Vitro Techniques ; Liposomes ; Mice ; Skin Absorption ; beta-Cyclodextrins

OBJECTIVETo observe cerebral protective effect of muscone (nasal administration) on traumatic brain injury model rats.

METHODSSD rats were divided into the sham-operation group, the model group, and the treatment groups according to random digit table, 50 in each group. Traumatic brain injury model was established by controlled cortical strike. Rats in the sham-operation group received surgery and anesthesia procedures only, with no strike. Muscone (1.8 mg/kg) was delivered to rats in the treatment group using in situ nasal perfusion, 30 min each time, twice daily for 7 successive days. Water content of brain tissue was detected in each group before intervention (T1), at day 3 of intervention (T2), day 5 of intervention (T3), and after intervention (T4), respectively. Expression levels of brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were detected using immunohistochemical analysis.

RESULTSCompared with the sham-operated group, water content of brain tissue increased (P < 0.05), and expression levels of NGF and BDNF decreased in the model group at T1, T2, T3, and T4 (P <0. 01). Compared with the model group, water content of brain tissue decreased (P < 0.05), and expression levels of NGF and BDNF increased (P < 0.01) in the treatment group at T1, T2, and T3.

CONCLUSIONNasal administration of muscone could reduce water content of brain tissue, alleviate cerebral edema, promote secretion of BDNF and NGF by olfactory ensheathing cells in traumatic brain injury rats.

Animals ; Brain ; drug effects ; Brain Injuries ; drug therapy ; Brain-Derived Neurotrophic Factor ; metabolism ; Cycloparaffins ; pharmacology ; Nerve Growth Factor ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo establish the method for determining muscone in rat intestinal perfusate by GC-MS/MS and study its intestinal absorption kinetic characteristics in rats.

METHODThe GC-MS/MS method was used to determine the content of muscone in rat intestinal circulation fluid. In situ intestinal circulation perfusion was adopted to study absorption kinetics of muscone in rats.

RESULTMuscone was proved to be well absorbed in each section of small intestine. Its absorption rate constants (Ka) and the absorption rate (A) in the rat intestine showed duodenum > jejunum (P < 0.05) , duodenum > ileum (P < 0.01). Its Ka, A and t1/2 in rat small intestine was 0.990 h(-1) , 43.58% and 0.705h, respectively.

CONCLUSIONMuscone was well absorbed in each intestinal section, with duodenum better than jejunum (Ka, T1/2, P < 0.05) significantly better than ileum (Ka, T1/2, P < 0.01; A, P < 0.05). There is no obvious statistical difference between jejunum and ileum.

Animals ; Chromatography, Gas ; methods ; Cycloparaffins ; analysis ; pharmacokinetics ; Intestinal Absorption ; drug effects ; Intestines ; drug effects ; metabolism ; Perfusion ; Rats ; Rats, Wistar ; Tandem Mass Spectrometry ; methods

OBJECTIVE: The present study aimed to determine the intracellular action of the antidepressant, venlafaxine, in C6 glioma cells using heat shock protein 70 (HSP70) immunocytochemistry and HSP70 Western blots; HSP70 is known to be associated with stress and depression. METHODS: The extent of HSP70 expression was measured after rat C6 glioma cells were treated with 1) dexamethasone only, 2) venlafaxine only, 3) simultaneous venlafaxine and dexamethasone, or 4) dexamethasone after venlafaxine pretreatment. Dexamethasone (10 microM, 6 hours) did not affect the level of HSP70 expression relative to control. RESULTS: Short-term (1 hour) venlafaxine treatment significantly increased the level of HSP 70 expression. Simultaneous long-term (72 hours) venlafaxine and dexamethasone treatment significantly reduced the level of HSP70 expression. Dexamethasone treatment administered following long-term (24 and 72 hours) pretreatment with venlafaxine also significantly reduced the level of HSP70 expression. CONCLUSION: Short-term treatment with venlafaxine increases the expression of HSP70, but prolonged treatment with dexamethasone suppresses the venlafaxine-induced expression of HSP70. These findings suggest that HSP70 and dexamethasone play a significant role in the pathophysiology of depression.
Animals ; Cyclohexanols ; Depression ; Dexamethasone ; Glioma ; Heat-Shock Proteins ; HSP70 Heat-Shock Proteins ; Immunohistochemistry ; Rats ; Venlafaxine Hydrochloride