Pharmacodynamic study of chiral oxiracetam on neuroprotection and anti-dementia / 药学学报

To compare the neuroprotective and anti-dementia pharmacological effects of chiral oxiracetam, glutamate and calcium ions were used to establish neuronal injury models in vitro, and the protective effects of chiral oxiracetam on primary neurons were assayed by MTT. Permanent bilateral common carotid artery occlusion (2-VO)-induced rats were randomly divided into sham group, model group, galantamine 3 mg‧kg-1 group, oxiracetam groups (30, 100 and 200 mg‧kg-1), S-oxiracetam groups (30, 100 and 200 mg‧kg-1) and R-oxiracetam 200 mg‧kg-1 group. The animal experiments in the present study were performed in accordance with the Ethical Guidelines of the Laboratory Animal Welfare Ethical Committee of Peking Union Medical College. Morris water maze and step-down test were applied to evaluate the cognitive dysfunction induced by cerebral hypoperfusion in rats. Oxiracetam, S-oxiracetam and R-oxiracetam exerted protective effects on primary neuronal damage caused by various stimuli, and oxiracetam and S-oxiracetam showed better neuro-protective effects. Morris water maze and step-down results showed that oxiracetam, S-oxiracetam and R-oxiracetam improved the cognition of 2-VO rats. In summary, S-oxiracetam exerted a better neuro-protective effect than oxiracetam and R-oxiracetam.

Qualitative and quantitative assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream by HPLC-TOF-MS and HPLC / 药物分析学报

Related substances in pharmaceutical formulations are associated with their safety, efficacy and stability. However, there is no overall study already published on the assessment of related substances in the Compound Ketoconazole and Clobetasol Propionate Cream. In this work, a reliable HPLC-TOF-MS qua-litative method was developed for the analysis of related substances in this preparation with a quick and easy extraction procedure. Besides the active pharmaceutical ingredients, two compounds named ke-toconazole impurity B′ optical isomer and ketoconazole impurity E were identified. Furthermore, a new HPLC method for qualitative and quantitative assessment on related substances and degradation pro-ducts, which were found in the stability test, was established and validated. The single standard to determine multi-components method was applied in the quantitative analysis, which was an effective way for reducing cost and improving accuracy. This study can provide a creative idea for routine analysis of quality control of the Compound Ketoconazole and Clobetasol Propionate Cream.

Study on the Molecular Docking of Penehyclidine Optical Isomers and Muscarinic Receptor Subtypes / 中国药房

OBJECTIVE:To study the affinity of penehyclidine optical isomers to muscarinic(M)receptor subtypes,and pro-vide reference for revealing the action targets and efficacy selectivity of penehyclidine. METHODS:Homology modeling,molecu-lar docking and other molecular simulation technologies were used to analyze and predict the binding energy of 4 optical isomers to M receptor subtypes and judge its affinity by comparing the binding energy of different optical isomers R1 (3R,2′R),R2 (3R, 2′S),S1(3S,2′R),S2(3S,2′S)with M receptor subtypes M1-M5. RESULTS:All the 4 optical isomers can dock into the ac-tive sites of M receptor subtypes,and different optical isomers showed great differences in the molecular docking with different M receptor subtypes. Penehyclidine isomers showed larger binding energy to M3,the binding energy of 4 optical isomers ranged in 5736.519-5907.143 kcal/mol. The binding energy of R1 to M1 was 1190.041 kcal/mol;while those of other optical isomers to each receptor subtype were lower or negative. CONCLUSIONS:R1 shows the affinity to M1 receptor. And all the 4 optical isomer show the affinity to M3.

Determination of three optical isomer impurities in (R,R)-penehyclidine fumarate by reversed phase high performance liquid chromatography with cyclodetrin as a moble phase additive / 中国药学杂志

OBJECTIVE: To establish a reversed phase high performance liquid chromatography (RP-HPLC) method for the chiral separation and determination of (R,R)-penehyclidine fumarate and its optical isomer impurities. METHODS: The chiral separation was performed on a C18 (4.6 mm × 250 mm, 5 μm) with mobile phase consisting of acetonitrile -0.05 mol · L-1 phosphates buffer (0.015 mol · L-1 β-cyclodextrin, 0.6% triethylamine, pH 2.3) at flow rate of 1.0 mL · min-1. The column temperature was set at 25°C. UV Detection wavelength was set at 206 nm. RESULTS: The limit of detection (LOD) of three optical isomers was 0.09%. The established chiral HPLC method was used for the quality control of (R,R)-penehyclidine fumarate. CONCLUSION: The method can be used to check and control the optical isomer impurities in the chiral drug, (R,R)-penehyclidine fumarate.

Effects of methotrexate enantiomers on ECV304 cell inhibition and its mechanisms / 中国药理学通报

Aim To investigate the effect of MTX(included(±)MTX,(+)MTX and(-)MTX)on the proliferation of ECV304 cells and to explore its mechanisms.Methods ECV304 cells were cultured.The cell proliferation was determined by MTT.The morphological changes were inspected by inverted microscope.Cell cycle phases were assayed by propidium iodide staining flow cytometry.Results ECV304 cells were treated with(+)MTX,(-)MTX and(±)MTX at 1～150 μmol·L~(-1) for 24,48,72 h.The results showed that the proliferation of ECV304 cells was significantly inhibited under different conditions.The order of the inhibited efficacy was(+)MTX>(±)MTX>(-)MTX.The morphology of ECV304 cells were changed by(+)MTX,(-)MTX and(±)MTX treatment,which included the cell shrinkage,chromatin condensation.After administration of 10 μmol·L~(-1) of(+)MTX,(-)MTX and(±)MTX for 48 h,the cell cycle phases were assayed by propidium iodide staining flow cytometry.The result showed DNA replication was interfered by(+)MTX,(-)MTX and(±)MTX treatment.Conclusions The proliferation of ECV304 cells has the chiral selective effects by(+)MTX and(-)MTX treatment,and the inhibition on ECV304 cells proliferation of(+)MTX is significantly stronger than that of (-)MTX.

MECHANISM OF ANTIFERTILITY BY GOSSYPOL OPTICAL ISOMERS IN RATS / 解剖学报

12 kinds of histochemical methods were adopted to evaluate the effects of gossypol optical isomers on the reproductive system of Wistar rats, following the administration of (?) and (+)-gossypol at a dosage of 30mg/kg daily, and(-)-gossypol at a dosage of 15 mg/kg daily, respectively for 2 or 3 weeks. (+)-gossypol has no an tifertility activity. (?) and (-)-gossypol caused kinetic disorder of spermatogemsis, and inhibited turnover of nuclear basic protein of the late, elongated spermatids in the testis. No changes in G6PDH and 30-HSDH histochmical reaction in Leydig cells, and ALP in the basement membrane of epididymis were observable reflecting that gossypol has no effect on synthesis and secretion of testosterone. Spermatozoa in the epididymis of rats treated with (?) and (-)-gossypol exhibited head and tail separation. The formazan deposits of reaction of LDH, LDH-X, MDH and ICDH located in sperm mitochondria appeared to become coarse and to reduce in quantity after (?) and (-)-gossypol treatment.