氟伐他汀钠缓释片的制备及其Beagle犬体内药动学研究

目的 制备氟伐他汀钠缓释片,进行体外释放特性以及Beagle犬体内药动学研究。方法 以羟丙甲纤维素为缓释材料制备氟伐他汀钠缓释片,测定其体外释放度和Beagle犬口服单剂量及多剂量后的血药浓度,推算药动学参数。结果 制备的氟伐他汀钠缓释片体外释放行为相似,口服单剂量和多剂量药动学参数C_max分别为（3 304.23±1 043.30）μg·L^-1和（3 760.86±754.77）μg·L^-1,T_1/2分别为（7.37±4.09）h和（6.04±2.63）h,AUC_（0-t）分别为（15 052.91±3 878.01）μg·L^-1和（15 374.91±2 712.20）μg·h·L^-1。结论 制备的氟伐他汀钠缓释片具有较明显的缓释效果,多次给药未出现明显的蓄积现象,表现出良好的安全性。     

冰片修饰的姜黄素阳离子脂质体的制备及其脑靶向作用研究

目的 制备冰片修饰的姜黄素阳离子脂质体（curcumin-loaded modifying borneol cationic liposomes，Cur-BCLPs），鼻腔给药后考察其在大鼠体内的药动学行为并对其脑组织分布进行研究。方法 采用乙醇注入法制备Cur-BCLPs；透射电镜观察阳离子脂质体的形态；激光粒度仪考察粒径；超速离心法测定其包封率及载药量；以姜黄素混悬液（curcumin suspension，Cur-Sol）和冰片-姜黄素混悬液（borneol curcumin suspension，BO-Cur-Sol）为对照组，考察大鼠鼻腔给药Cur-BCLPs的体内药动学过程，并测定其在大鼠脑组织的浓度，运用DAS 2.0软件拟合药动学参数。结果 阳离子脂质体外观呈圆形或类圆形，平均粒径为（105.99±2.40）nm，包封率和载药量分别为（81.95±1.03）%和（4.28±0.46）%；体内药动学结果显示，Cur-Sol、BO-Cur-Sol和Cur-BCLPs的半衰期（T_1/2）分别为（4.27±1.53）h，（3.98±0.24）h和（6.01±0.63）h，AUC_0→t分别为（224.38±21.95）μg·h·L^-1，（243.40±12.26）μg·h·L^-1和（562.28±24.30）μg·h·L^-1，清除率分别为（1.82±0.36）L·h^-1·kg^-1，（1.72±0.11）L·h^-1·kg^-1和（0.78±0.03）L·h^-1·kg^-1，滞留时间分别为（4.28±0.23）h，（4.41±0.15）h和（8.09±0.17）h。脑组织分布结果显示，Cur-Sol、BO-Cur-Sol和Cur-BCLPs的AUC_0→t分别为（29.82±1.10）μg·h·g^-1，（35.47±1.75）μg·h·g^-1和（54.06±3.90）μg·h·g^-1，清除率分别为（15.73±0.84）L·h^-1·kg^-1，（13.23±0.52）L·h^-1·kg^-1和（8.52±0.92）L·h^-1·kg^-1。结论 Cur-BCLPs经鼻腔给药后显著提高姜黄素体内和脑组织蓄积量并且延缓消除。     

盐酸阿霉素聚乳酸纳米粒的制备及大鼠体内药动学研究

目的 优化盐酸阿霉素聚乳酸纳米粒（DOX-PLA-NPs）的制备工艺,并对其理化性质、体外释放及大鼠体内药动学进行研究。方法 采用改良的复乳-溶剂挥发法制备DOX-PLA-NPs,正交设计优化其处方工艺,对其纳米粒形态、粒径、Zeta电位、包封率与载药量进行测定。以DOX原药为对照组,考察DOX-PLA-NPs的体外释药特性及大鼠尾静脉给药后的体内药动学参数。结果 DOX-PLA-NPs外观圆整,平均粒径为（125.67±3.80） nm、Zeta电位为（-35.97±1.58） mV、包封率和载药量分别为（81.23±1.46）%,（10.29±0.63）%。体外释放结果显示,DOX经纳米粒包裹后,具明显的缓释作用。DOX原药和纳米粒的体内药动学过程均符合开放式二室模型,t_1/2β分别为（1.15±0.175） h、（6.43±2.12） h,CL分别为（174.76±47.22） h·L^-1、（30.68±11.86） h·L^-1,AUC_0→t分别为（6.01±1.61）μg·h·L^-1、（36.04±13.72）μg·h·L^-1。结论 制备的盐酸阿霉素聚乳酸纳米粒粒径较小、包封率较高,具明显的缓释作用,并能提高药物的生物利用度。     

老年重症耐甲氧西林金黄色葡萄球菌感染患者替考拉宁的药动学研究和药效学评价

目的 探讨耐甲氧西林金黄色葡萄球菌（methicillin-resistant Staphylococcus aureus，MRSA）肺部感染老年患者替考拉宁的药动学差异与药效学评价。方法 研究纳入2018年9月—2019年8月诊断为MRSA肺部感染患者50例，治疗前下呼吸道痰液标本培养提示为MRSA感染并对替考拉宁敏感。所有患者予静脉输注替考拉宁，前3剂400 mg，每12 h给药1次，维持剂量400 mg每24 h给药1次。将达到稳态后第5次给药前测得C_min≤10 μg·mL^-1的患者维持剂量方案更改为600 mg qd。注射用替考拉宁400 mg或600 mg溶于100 mL 0.9%氯化钠注射液，给药时间为30 min，疗程为14~21 d。按规定时间采集静脉血2 mL，采用HPLC检测血药浓度，使用DAS 3.0软件处理，求出各例患者的药动学参数。将达稳态后第5次给药前测得C_min>10 μg·mL^-1的药动学参数设为A；对于C_min≤10 μg·mL^-1的患者，将维持剂量调整为600 mg qd，并将调整剂量后第5次给药前测得C_min>10 μg·mL^-1的药动学参数设为B。按照APACHE II评分和SOFA评分将患者分为重症和非重症2组。结合PK/PD原理，比较2组患者在C_min处于10~20 μg·mL^-1和20~30 μg·mL^-1以及AUC/MIC≥345和<345的临床治疗有效率、细菌清除率及不良反应发生情况。结果 替考拉宁药动学以二室模型描述最佳。负荷剂量相同时，维持剂量为400 mg的A组与维持剂量为600 mg的B组药动学参数比较如下：C_max[（32.28±15.16） mg·L^-1vs（65.73±28.96） mg·L^-1]，t_1/2[（86.24±10.61） h vs（70.51±11.78） h]，V_d[（2.73±1.32） L·kg^-1vs（2.58±1.02） L·kg^-1]，CL[（0.11±0.05） L·h^-1·kg^-1vs（0.13±0.06） L·h^-1·kg^-1]，AUC_（0~t）[（2 698.16±1 603.25） mg·h·L^-1vs（4 076.85±1 873.09） mg·h·L^-1]，AUC_（0~∞）[（4 509.33±2 786.54） mg·h·L^-1vs（7 193.58±4 109.81） mg·h·L^-1]，差异有统计学意义（P<0.05）。患者SOFA评分≤5和>5的临床有效率为65.71%和53.33%，细菌清除率分别为65.79%和47.37%。APACHEII评分≤15和>15的临床有效率分别为63.64%和58.82%，细菌清除率分别为63.16%和52.63%。结论 MRSA肺部感染老年患者替考拉宁的药动学存在较大差异，结合PK/PD原理，能够为个体化治疗提供科学的给药方案。     

丙戊酸钠和丙戊酸镁在大鼠体内的药动学研究

目的 研究丙戊酸钠和丙戊酸镁在大鼠体内的药动学特征,评价其优势丙戊酸盐,为临床合理用药提供参考。方法 SD大鼠随机分为2组,分别灌胃给予丙戊酸钠片和丙戊酸镁片。于不同时间点眼眶取血。采用HPLC测定血清中丙戊酸的血药浓度,计算2种丙戊酸盐在大鼠体内的药动学参数,并比较2种丙戊酸盐之间的差异。结果 HPLC测定丙戊酸血药浓度方法专属性好,血清丙戊酸浓度在10.00~110.00 μg·mL^-1内线性关系良好。精密度、稳定性和回收率均符合要求。丙戊酸钠和丙戊酸镁在大鼠体内的主要药动学参数：T_1/2分别为（14.02±3.86） h和（12.11±1.95） h;T_max分别为（3.67±0.58） h和（2.67±0.26） h;C_max分别为（67.10±10.87）μg·mL^-1和（75.67±12.94）μg·mL^-1;AUC_（0-t）分别为（969.86±72.08）μg·mL^-1·h和（1 093.56±48.69）μg·mL^-1·h;AUC_（0-∞）分别为（1 178.10±185.29）μg·mL^-1·h和（1 279.35±109.18）μg·mL^-1·h;MRT_0-t分别为（10.73±2.05） h和（13.06±3.24） h。V_d分别为（16.31±2.18） L和（23.47±2.19） L;CL分别为（0.056 3±0.009） L·h^-1和（0.051 1±0.004） L·h^-1。结论 与丙戊酸钠相比,丙戊酸镁在大鼠体内的药动学参数具有一定的优势,可能是一种更具有治疗优势的丙戊酸盐。     

UPLC-MS/MS快速测定大鼠血浆中盐酸美沙酮及其代谢产物含量

目的 建立超高效液相色谱-串联质谱（UPLC-MS/MS）测定大鼠血浆中盐酸美沙酮及其代谢产物乙二胺二甲基次磷酸（2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine,EDDP）的含量。方法 以地西泮为内标,大鼠血浆用乙腈沉淀蛋白,运用UPLC-MS/MS检测大鼠灌胃盐酸美沙酮6 mg·kg^-1后血浆中美沙酮和EDDP的血药浓度,并对数据进行分析。结果 大鼠血浆中盐酸美沙酮和EDDP的定量限均为0.5 ng·mL^-1;线性相关系数r>0.999;日内精密度和日间精密度的RSD均<15%;绝对回收率均>85%,相对回收率在90%~110%之间;基质效应在92.80%~97.71%之间。主要药动学参数：美沙酮、EDDP在大鼠血浆中的消除半衰期（t_1/2）为（1.479±0.839）,（2.590±0.760）h;最高血药浓度（C_max）为（48.562±10.501）,（25.542±3.706）μg·L^-1;平均滞留时间（MRT_0-t）为（3.476±0.310）,（3.883±0.514）h;曲线下面积（AUC_0-t）为（204.036±61.145）,（86.031±15.287）μg·h·L^-1;清除率（CL）为（32.338±14.343）、（70.137±10.786）L·h^-1·kg^-1,各项药动学参数比较差异均有统计学意义。结论 该法专属性强、分离完全、快速灵敏,适用于大鼠血浆中盐酸美沙酮及其代谢产物EDDP的含量测定和药动学研究。     

左乙拉西坦缓释片的制备及其Beagle犬体内药动学研究

目的 制备左乙拉西坦缓释片,进行体外释放特性以及Beagle犬体内药动学研究。方法 按照筛选处方制备左乙拉西坦缓释片,以市售左乙拉西坦缓释片（Keppra-XR）为参比制剂,采用相似因子（f₂）法进行体外释放行为相似度评价;并将自制左乙拉西坦缓释片与市售普通片进行Beagle犬体内药动学参数比较。结果 自制左乙拉西坦缓释片与市售左乙拉西坦缓释片体外释放行为相似。市售左乙拉西坦普通片和自制左乙拉西坦缓释片的药动学参数T_max分别为（1.75±0.50）和（5.50±1.00）h,C_max分别为（30.33±2.00）和（17.29±3.56）mg·L^-1,AUC_0-t分别为（186.88±8.83）和（202.50±34.20）mg·L^-1·h。结论 自制的左乙拉西坦缓释片具有缓释效果。     

柱前衍生-HPLC测定白消安在家兔体内的药动学参数

目的 建立测定家兔血清中白消安浓度和家兔体内药动学特征的柱前衍生化HPLC。方法 以1,5-戊二醇二甲磺酸酯为内标,二乙基二硫代氨基甲酸钠为衍生化试剂。流动相：甲醇-水（54∶46）,流速：0~20 min（1.0 mL·min^-1）,20~27 min（1.3 mL·min^-1）。柱温：30℃,检测波长：280 nm,进样量：25 μL。家兔分别以灌胃、静注的方式给予白消安,按本法测定血药浓度,DAS 3.0计算药动学参数。结果 白消安的血药浓度在0.1~3.4 mg·-L¹ 内线性关系良好（r=0.999 7）,日内、日间精密度以及样品稳定性符合中国药典2015年版的规定。低、中、高浓度的萃取回收率分别为90.0%,89.0%,91.5%。不同给药途径获得的药动学参数：单剂量口服t_1/2=（2.26±0.66）h,k=（0.33±0.12）·h^-1,k_a=（2.54±1.3）·h^-1,AUC_0–t=（1.95±0.18）h·mg·mL^-1;单剂量静脉注射t_1/2=（1.53±0.09）h,k=（0.45±0.03）·h^-1,AUC_0–∞=（4.38±0.26）h·mg·mL^-1。多剂量口服后C_ss=（0.48±0.03）mg·mL^-1,AUC_0–τ=（3.87±0.26）h·mg·mL^-1。结论 建立的柱前衍生-HPLC法适用于白消安血药浓度测定及药动学研究,不同给药途径的药动学参数为临床药动学研究提供了依据。     

LC-MS/MS测定阿齐沙坦及其盐在大鼠血浆中的药动学研究

目的 建立液相色谱-串联质谱法测定大鼠血浆中阿齐沙坦及其盐的浓度并研究其药动学。方法 大鼠血浆样本以乙腈沉淀蛋白后,采用Eclipse Plus C₁₈色谱柱（50 mm×3.0 mm,1.8 μm）;流动相（乙腈：水=60：40）,流速为0.35 mL·min^-1,柱温为40℃;采用Agilent 6430三重四极杆串联质谱仪,离子化方式：电喷雾-正离子（API-ES）;监测方式：MRM;阿齐沙坦监测离子对457.3/233.1,缬沙坦监测离子对436.2/291.4,用作内标。SD大鼠灌胃给予阿齐沙坦1.0 mg·kg^-1及阿齐沙坦盐1.2 mg·kg^-1。结果 阿齐沙坦在5~30 000 ng·mL^-1内线性关系良好;回收率为85%~115%,精密度RSD在±15%内。阿齐沙坦盐大鼠体内主要动力学参数如下：AUC_{（0-24 h）}为（12.9±3.2）μg·mL^-1·h^-1,AUC_（0-∞）为（14.2±4.1）μg·mL^-1·h^-1,C_max为（3.8±0.3）μg·mL^-1,T_1/2为（13.4±0.5）h。阿齐沙坦的主要动力学参数如下：AUC_{（0-24 h）}为（8.1±2.6）μg·mL^-1·h^-1,AUC_（0-∞）为（9.7±3.1）μg·mL^-1·h^-1,C_max为（2.3±0.5）μg·mL^-1,T_1/2为（10.5±0.5）h。结论 本法经方法学验证,适用于大鼠血浆中阿齐沙坦及其盐的浓度测定,可用于阿齐沙坦及其盐大鼠体内药动学研究。     

UPLC-MS/MS检测大鼠血浆中阿帕替尼的浓度及其药动学研究

目的 采用UPLC-MS/MS建立快速检测大鼠血浆中阿帕替尼浓度的方法,并应用于药动学研究。方法 大鼠血浆样本用乙腈沉淀蛋白,液质联用技术检测浓度,流动相为乙腈-水（含0.1%甲酸）,梯度洗脱,流速为0.3 mL·min^-1,柱温40℃,内标为氯唑沙宗;质谱条件：电喷雾离子化源（ESI）,负离子监测模式,检测离子对阿帕替尼为m/z 396.2→210.0和m/z 396.2→158.0,氯唑沙宗m/z 168.0→132.0。结果 阿帕替尼和内标氯唑沙宗的保留时间分别为1.07 min和1.40 min,线性范围为10~2 000 ng·mL^-1（r²=0.993）,检测限为1 ng·mL^-1,准确度为90.65%~111.50%,基质效应为89.14%~104.65%,平均回收率>86%,日内、日间精密度RSD均<10%。常温下放置24 h、冻融2次和-80℃冻存30 d的RSD均<10%。药动学研究结果显示,大鼠单次灌胃阿帕替尼76.5 mg·kg^-1,AUC_（0-t）为（6 114.41±645.99）ng·mL^-1·h,CL_z/F为（12.21±1.08）L·h^-1·kg^-1,V_z/F为（75.70±38）L·kg^-1,T_1/2为（4.23±1.94）h,T_max为（2±0.71）h,C_max为（1 377.7±284.54）μg·L^-1。结论 该法操作简便,重复性好,准确可靠,适用于大鼠血浆中阿帕替尼的浓度检测及其药动学研究。     

Synthesis and evaluation of 2,6-piperidinedione derivatives as potentially novel compounds with analgesic and other CNS activities

New 2,6-piperidinediones 2_a–g and 4_a–d were prepared by initial condensation of aromatic aldehydes or cycloalkanones with cyanoacetamide to give α-cyanocinnamides l_a–g or cycloalkylidenes 3_a,b which underwent Michae1 addition with ethyl cyanoacetate or diethylmalonate. Compounds 4_a–d were alkylated by various alkyl halides to produce the N-alkylated 2,6-piperidinedione derivatives 5_a–m. Some new selected compounds 2_a–c,f, 4_a–d & 5_e,h,j were pharmacologically evaluated for potential anticonvulsant, sedative and analgesic activities. These compounds exhibited significant anticonvulsant and analgesic effects after a single I.P. administration 100 mg/kg b.wt. . On the other hand all the investigated compounds induced hypnotic activity and prolonged the phenobarbital sodium- induced sleep as compared with the control group and the most potent compound was found to be 2_f.     

NEURAMIDE STIMULATES ADRENOCORTICOTROPIN BUT NOT PROLACTIN RELEASE FROM RAT PITUITARY

Neuramide (NMD), a substance found in crude preparations of porcine stomach extract, is a viral inhibitor that also has putative immunostimulatory effects. The effects of NMD on stress-hormone (ACTH and prolactin—PRL) release were assessed inin vivoandin vitrostudies. In the former, blood levels of corticosterone and PRL were measured in NMD-treated male rats.In vitroexperiments were performed to evaluate the effects of NMD and three of its fractions (obtained with high performance liquid chromatography) on ACTH and PRL release from perfused rat pituitary slices. NMD increased plasma corticosterone levelsin vivoand produced dose-dependent increases inin vitropituitary release of ACTH. No effects on PRL secretion were observedin vivoorin vitro. The stimulatory effects on ACTH release were caused by the NMD fraction with a molecular weight of >5000<10000Da.     

鼻渊净胶囊的HPLC指纹图谱研究

目的 建立鼻渊净胶囊的高效液相色谱（HPLC）指纹图谱。方法 采用Agilent SB-C₁₈（4.6 mm×250 mm,5 μm）色谱柱,乙腈-水为流动相、以1.0 ml/min流速行梯度洗脱,检测波长210 nm,柱温30 ℃,洗脱时间为80 min。采用中药色谱指纹图谱相似度评价系统（2004A版）对检测出色谱进行指纹图谱相似度评价。结果 建立了鼻渊净胶囊的HPLC指纹图谱,确定了20个共有峰,15个峰归属到各药材,其中5个峰确认了化学成分;10批样品的指纹图谱的整体相似度与对照图谱比较,均在90%以上。结论 所建立的鼻渊净胶囊指纹图谱有助于从整体上控制该制剂的质量。     

Investigation of the prevalence of tetQ, tetX and tetX1 genes in Bacteroides strains with elevated tigecycline minimum inhibitory concentrations

In this study, the antibiotic susceptibilities to tigecycline and tetracycline of 35 selected Bacteroides fragilis group strains were determined by Etest, and the presence of tetQ, tetX, tetX1 and ermF genes was investigated by polymerase chain reaction (PCR). tetQ was detected in all 12 B. fragilis group isolates (100%) exhibiting elevated tigecycline minimum inhibitory concentrations (MICs) (≥8 μg/mL) as well as the 8 strains (100%) with a tigecycline MIC of 4 μg/mL, whilst tetX and tetX1 were present in 15% and 75% of these strains, respectively. All of these strains were fully resistant to tetracycline (MIC ≥ 16 μg/mL). On the other hand, amongst the group of strains with tigecycline MICs < 4 μg/mL (15 isolates), tetQ, tetX and tetX1 were found less frequently (73.3%, 13.3% and 46.7%, respectively). All but two strains harbouring the tetQ gene in this group were non-susceptible to tetracycline, with a MIC > 4 μg/mL. These data suggest that in most cases tigecycline overcomes the tetracycline resistance mechanisms frequently observed in Bacteroides strains. However, the presence of tetX and tetX1 genes in some of the strains exhibiting elevated MICs for tigecycline draws attention to the possible development and spread of resistance to this antibiotic agent amongst Bacteroides strains. The common occurrence of ermF, tetX, tetX1 and tetQ genes together predicted the presence of the CTnDOT-like Bacteroides conjugative transposon in this collection of Bacteroides strains.     

EFFECT OF POLICOSANOL SUCCESSIVE DOSE INCREASES ON PLATELET AGGREGATION IN HEALTHY VOLUNTEERS

Policosanol is a cholesterol-lowering drug with hypocholesterolemic effects demonstrated in experimental models, healthy volunteers and type II hypercholesterolemic patients. In addition, antiplatelet effects of policosanol have been shown in experimental models and healthy volunteers. The effect of successively increasing doses of policosanol on platelet aggregation was investigated in a randomized, placebo-controlled, double-blind study conducted in 37 healthy volunteers. The volunteers were on a placebo-baseline period (two tablets per day) for 7 days and thereafter they received randomly, under double-blind conditions, placebo or policosanol (10mgday⁻¹) for 7 days. After this period dosage was doubled to 20mgday⁻¹for the next 7 days and then again doubled to 40mgday⁻¹, while the control group received placebo tablets all the time. Platelet aggregation as well as coagulation time was measured at baseline and after each dosing step. Results showed that antiplatelet effects of policosanol were successfully enhanced throughout the study, thus suggesting a dose-dependent relationship. No significant effect was reached during the first dosing period, but significant reductions of epinephrine and ADP-induced platelet aggregation were observed after the second one. Finally, a significant inhibition of platelet aggregation induced by all the agonists was observed at the last dosing step. Coagulation time remained unchanged during the trial.     

喙果黑面神化学成分研究

目的研究大戟科植物喙果黑面神(Breynia rostrata Merr.)的化学成分。方法利用硅胶、凝胶等色谱技术分离纯化化学成分,根据化合物的理化性质和光谱数据进行结构鉴定。结果从喙果黑面神的正丁醇萃取部分分离得到4个化合物,分别鉴定为6-O-甲基丙酰基-α-D-吡喃葡糖(6-O-methylpropanoyl-α-D-glucopyranose,1);4″-苯酚基-6-O-甲基丙酰基-β-D-吡喃葡糖苷(4″-phenolic-6-O-methylpropanoyl-β-D-glucopyranoside,2);1-O-没食子酰基-β-D-吡喃葡糖苷(1-O-galloyl-β-D-glucopyranoside,3);熊果苷(arbutin,4)。结论化合物1和2为新化合物,3和4均为首次从该种植物分离得到。     

AMELIORIATION OF CHEMICALLY-INDUCED HEPATOCYTE INJURY BY CYCLOSPORINE A

Cyclosporine A, beside its current applications, possesses potential hepatoprotective effects. This study was directed to investigate the effect of Cyclosporine A pretreatment on hepatic injury due to carbon tetrachloride (CCl₄) and -galactosamine. Rats were injected by two successive doses of Cyclosporine A (5mgkg⁻¹day⁻¹). Six hours after the second dose, 1mlkg⁻¹of CCl₄was administered i.p. Effects associated with Cyclosporine A pretreatment were examined by using isolated hepatocytes and hepatocytes that were immobilized and continuously perfused. -Galactosamine (5m ) was added directly to the perfusion medium. After isolation, hepatocytes were examined histologically by light and electron microscopy, immobilized and perfused for further metabolic functional activity evaluation. Cyclosporine A pretreatmentin vivoproduced hepatoameliorative effects of various degrees which were statistically significant as manifested by: (1) an increased trypan blue exclusion after CCl₄; (2) an improved ureagenesis after CCl₄; (3) a reduction in the lipid droplets accumulation in the cytoplasm produced by CCl₄administration; (4) well preserved cytoplasmic organelles as mitochondria, endoplasmic reticulum ER, nuclear chromatin structures that were altered by CCl₄; and (5) an increased hepatocytes survival in the agarose gel matrix, reduction of LD leakage and improvement of ureagenesis after -galactosamine addition to the perfusion medium. The beneficial effect of Cyclosporine A pretreatment in modifying hepatotoxicity of chemical insults merits further studies.     

EFFECTS OF 2-GUANIDINE-4-METHYLQUINAZOLINE ON GASTRIC ACID SECRETION IN RATS

In this study 2-guanidine-4-methylquinazoline (2-GMQ) appeared to decrease basal and stimulated gastric acid secretion, while structurally related compounds as dimethyl- biguanide, cyanoguanidine and 2-cyanoamino-4-methylpyrymidine did not. Thus, there is an antisecretory effect when the biguanide group is associated with a lipophilic structure. The antisecretive effects exerted by 2-GMQ are associated with anti H₂-histamine activity.The anti H₂-histamine nature of the effects of 2-GMQ was confirmed by the capacity of this compound of depressing the chronotropic activity of the isolated guinea pig auricle increased by histamine, as well as relaxant activity in rat uterus contracted by histamine, since both preparations are rich in H₂-histamine receptors.     

栝楼不同药用部位质量控制的研究进展

瓜蒌子、瓜蒌皮、瓜蒌、天花粉来源于栝楼的不同药用部位,4味药材均为常用的大宗药材,现行版《中国药典》对其制定的质量标准过于简单,无法科学合理地控制其质量。本文对瓜蒌子、瓜蒌皮、瓜蒌、天花粉安全性和有效组分的研究进行综述,明确了相关研究存在的问题并针对问题提出建议,为科学全面的药材及饮片标准的制定提供参考依据。     

Effect of bay K 8644, a calcium channel agonist,on dog cardiac muscarinic receptors

To investigate further whether the effects of the dihydropyridine (DHP) drugs on calcium channels are related to those of these drugs on muscarinic receptors, the binding characteristics of the DHP calcium channel agonist, Bay K 8644, on muscarinic receptors and calcium channels were compared to those of the DHP calcium channel antagonists, nicardipine and nimodipine in the dog cardiac sarcolemma. Bay K 8644, nicardipine and nimodipine inhibited the specific [³H]QNB binding with K _i values of 16.7μM, 3.5μM and 15.5μM respectively. Saturation data of [³H]QNB binding in the presence of these DHP drugs showed this inhibition to be competitive. Bay K 8644, like nicardipine and nimodipine, blocked the binding of [³H]nitrendipine to the high affinity DHP binding sites, but atropine did not, indicating that the muscarinic receptors and the DHP binding sites on calcium channels are distinct. The K _i value of Bay K 8644 for the DHP binding sites was 4 nM. Nicardipine and nimodipine (K _i :0.1–0.2 nM) were at least 20 times more potent than Bay K 8644 in inhibiting [³H]nitrendipine binding. Thus, the muscarinic receptors were about 4000 times less sensitive than these high affinity DHP binding sites to Bay K 8644. These results suggest that the DHP calcium agonist Bay K 8644 binds directly to the muscarinic receptors but its interaction with the muscarinic receptors is not related to its binding to the DHP binding sites on calcium channels.