JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2017
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IF 3.255
Wen-Peng Zhang,Dong-Ying Chen
The purpose of this work was to investigate the crystal structures and physicochemical properties of amisulpride polymorphs. Except of the previously reported polymorph (named as Form I), a new polymorphic form (named as Form II) was discovered through comprehensive solid-state screening experiments. Both polymorphic forms were characterized by single crystal X-ray structure analysis (SXRD), powder X-ray diffraction (PXRD), dynamic vapor sorption (DVS) and thermal analysis (TGA and DSC) as well. It has been found that the Forms I and II are of conformational polymorph with the main conformational difference around ethylsulfonyl group. Form II possesses lower hygroscopicity and better solubility compared with that of Form I, indicating Form II could be an alternate solid form for formulation development.
研究领域:
药学
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材料科学
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药物化学
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DOI
PubMed
高影响因子
BIOPHARMACEUTICS & DRUG DISPOSITION
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2017
·Vol. 38
·期 9
·526-534
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IF 2.091
Liping Li,Yayun Weng,Wei Wang,Mengru Bai,Hongmei Lei,Hui Zhou,Huidi Jiang
Sulpiride, a selective dopamine D2 receptor blocker, is used widely for the treatment of schizophrenia, depression and gastric/duodenal ulcers. Because the great majority of sulpiride is positively charged at physiological pH 7.4, and ~70% of the dose recovered in urine is in the unchanged form after human intravenous administration of sulpiride, it is believed that transporters play an important role in the renal excretion of sulpiride. The aim of the present study was to explore which transporters contribute to the renal disposition of sulpiride. The results demonstrated that sulpiride was a substrate of human carnitine/organic cation transporter 1 (hOCTN1) and 2 (hOCTN2), human organic cation transporter 2 (hOCT2), human multidrug and toxin efflux extrusion protein 1 (hMATE1) and 2-K (hMATE2-K). Sulpiride accumulation from the basolateral (BL) to the apical (AP) side in MDCK-hOCT2/pcDNA3.1 cell monolayers was much greater than that in MDCK-hOCT2/hMATE1 cells, and cimetidine dramatically reduced the intracellular accumulation of sulpiride from BL to AP. In addition, the accumulation of sulpiride in mouse primary renal tubular cells ( m PRTCs) was markedly reduced by inhibitors of Oct2 and Octns. The results implied that OCTN1, OCTN2, OCT2, MATE1 and MATE2-K probably contributed to the renal transfer of sulpiride, in which OCT2 mediated the uptake of sulpiride from the bloodstream to the proximal tubular cells, while MATEs contributed to the sulpiride efflux from the proximal tubular cells to the renal lumen, and OCTNs participated in both renal secretion and reabsorption.
研究领域:
药理学
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肾病学
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药物代谢
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
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IF 5.875
Liping Wang,Xuhui She,Zhi Chen,Sisi Quan,Yingtao Liu,Xiaoman Mai,Tiefeng Yuan,Huajun Fan
A novel molecularly imprinted polymer (MIP) with chiral recognition affinity to S-sulpiride (S-SUL) enantiomer was prepared by using newly synthesized N-acryloyl-tryptophan (ATrp) as function monomer , S-SUL as the template molecule, and ethyleneglycol dimethacrylate (EGDMA) as the cross linker. Under the optimized synthesis conditions, the MIP was synthesized by bulk polymerization according to the molar ratio of 1:4 of S-SUL to ATrp, and structurally characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM) and laser particle analysis. The results illustrated that the MIP offered uniform, loose and porous structure. The adsorption performance of the MIP was evaluated by the isotherm and kinetic models, and the adsorption isotherm conformed to the Freundlich model. The maximum adsorption capacity, selectivity factor and enantioselectivity coefficient to S-SUL were respectively 226.2389 µmol/g, 2.34 and 11.66. Based on the chiral recognition specificity, the drug release experiments demonstrated that the MIP as controlled and sustained release carrier could inhibit the release rate of S-enantiomer compared to the tablet without the MIP, exhibiting the potential of the MIP synthesized in chiral drug delivery.
研究领域:
药物化学
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材料科学
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制药工程
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
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2018
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IF 2.746
Junlei He,Jiahao Yuan,Juan Du,Xiaoguang Chen,Xinguo Zhang,Ande Ma,Jialiang Pan
An automated on-line solid-phase extraction (SPE) method coupled with high performance liquid chromatography (HPLC) was developed for the first application to rapid quantification of trace amisulpride in human plasma. A kind of restricted-access media (RAM) column (Capcell Pak MF Ph-1) was adopted for highly efficient extraction of amisulpride and meanwhile for the limited access of macromolecular matrices. It was robust and reusable for >1000 times. The utilization of two programmable pumps enabled the simultaneous execution of SPE and HPLC analysis within 10 min. Additionally, using appropriate valve-switching time was found to efficiently reduce the contamination of HPLC system caused by co-elution of impurity from an RAM column, facilitating continuous analysis of large-scale samples. The method was characterized by free of internal standard (IS), which exhibited low limit of detection (0.0035 μg·mL −1 ), satisfactory precision and accuracy (recoveries of 98.1%–104.6% with relative standard deviations below 4.6%). Amisulpride was successfully detected in the plasma samples originated from four patients. Notably, interindividual differences of plasma sample matrices did not yield an adverse effect on the accuracy of our IS-free method. The comparison to previous methods shows the superiority of the method in terms of sensitivity, IS requirement, speed, and automation. Thus, the method has great potential for the application to therapeutic drug monitoring as well as large-scale bioanalytical and clinical studies.
研究领域:
分析化学
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临床医学
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药物分析
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DOI
高影响因子
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
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2022
·Vol. 322
·期 3
·C327
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IF 5.282
Xiao-Yu Liu,Li-Fei Zheng,Yan-Yan Fan,Qian-Ying Shen,Yao Qi,Guang-Wen Li,Qi Sun,Yue Zhang,Xiao-Yan Feng,Jin-Xia Zhu
In vivo administration of dopamine (DA) receptor (DR)-related drugs modulate gastric pepsinogen secretion. However, DRs on gastric pepsinogen-secreting chief cells and DA D2 receptor (D2R) on somatostatin-secreting D cells were subsequently acquired. In this study, we aimed to further investigate the local effect of DA on gastric pepsinogen secretion through DRs expressed on chief cells or potential D2Rs expressed on D cells. To elucidate the modulation of DRs in gastric pepsinogen secretion, immunofluorescence staining, ex vivo incubation of gastric mucosa isolated from normal and D2R−/− mice were conducted, accompanied by measurements of pepsinogen or somatostatin levels using biochemical assays or enzyme-linked immunosorbent assays. D1R, D2R, and D5R-immunoreactivity (IR) were observed on chief cells in mouse gastric mucosa. D2R-IR was widely distributed on D cells from the corpus to the antrum. Ex vivo incubation results showed that DA and the D1-like receptor agonist SKF38393 increased pepsinogen secretion, which was blocked by the D1-like receptor antagonist SCH23390. However, D2-like receptor agonist quinpirole also significantly increased pepsinogen secretion, and D2-like receptor antagonist sulpiride blocked the promotion of DA. Besides, D2-like receptors exerted an inhibitory effect on somatostatin secretion, in contrast to their effect on pepsinogen secretion. Furthermore, D2R−/− mice showed much lower basal pepsinogen secretion but significantly increased somatostatin release and an increased number of D cells in gastric mucosa. Only SKF38393, not quinpirole, increased pepsinogen secretion in D2R−/− mice. DA promotes gastric pepsinogen secretion directly through D1-like receptors on chief cells and indirectly through D2R-mediated suppression of somatostatin release.
研究领域:
胃肠病学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2024
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IF 6.9
Yuan Liang,Yu Yang,Ruiyan Huang,Jiangyue Ning,Xingyan Bao,Zelong Yan,Haotian Chen,Li Ding,Chang Shu
Depression ranks as the fourth most prevalent global disease, with suicide incidents occurring at a younger age. Sulpiride (SUL), an atypical antidepressant drug acting as a dopamine D2 receptor antagonist and possessing anti-inflammatory properties, exhibits limited ability to penetrate the blood brain barrier (BBB). This weak penetration hampers its inhibitory effect on prolactin release in the pituitary gland, consequently leading to hyperprolactinemia. In order to enhance the central nervous system efficacy of sulpiride and reduce serum prolactin levels, we covalently linked sulpiride to VPALR derived from the nuclear DNA repair protein ku70. In vivo study on depressive mice using intraperitoneal injection of VPALR-SUL demonstrated a significant increase in struggle time and total distance compared to those treated with only sulpiride while also reducing serum prolactin concentration. The pharmacokinetic study results showed that VPALR-SUL prolonged half-life and increased bioavailability. In conclusion, VPALR-SUL exhibited potential for enhancing sulpiride transport across the BBB, augmenting its antidepressant effects, and reducing serum prolactin levels. This study laid a foundation for improving sulpiride delivery and developing novel antidepressants.
研究领域:
药理学
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神经科学
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分子生物学
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DOI
PubMed
高影响因子
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