口服5—单硝酸异山梨醇酯胶囊和进口片剂在健康志愿者的药代动力 …

目的；研究国产５－单硝酸异山梨醇酯（ＩＳ－５－ＭＮ）胶囊及进口ＩＳ－５－ＭＮ片剂在健康志愿者的药动学特征及其生物等效性。方法：随机双盲实验先后一次口服ＩＳ－５－ＭＮ胶囊和进口ＩＳ－５－ＭＮ参比片剂（２０ｍｇ）后，以市郊和气相色谱法时检测其血药浓度，采用ＣＡＰＰ软件包计算药动学参数，并做生物等效性分析。     

毛细管气相色谱—电子捕获法测定5—单硝酸异山梨醇酯血药浓度

目的：建立毛细管气相色谱－电子捕获法（GC－ECD）测定人血浆中5－单硝酸异山梨醇酯（5－IM）浓度的方法。方法：采用HP5890气相色谱仪，弹性石英毛细柱HP Ultral,^63Ni电子捕获检测器检测，内标为2－硝基氯化苯。结果：5－单硝酸异山梨醇酯的线性范围为8－800μg/L(r=0.9945),提取回收率大于97％，日内、日间相对偏差均小于5％。结论：本法操作简单易行，可用于血浆中5－IM浓度的测定。     

麝香保心丸联合单硝酸异山梨醇酯治疗心绞痛较单用效果好

目的探讨麝香保心丸联合单硝酸异山梨醇酯治疗缺血性心脏病心绞痛的效果。方法147例缺血性心脏病心绞痛患者随机分为麝香保心丸联合单硝酸异山梨醇酯治疗组,单用麝香保心丸组和单用单硝酸异山梨醇酯组。结果麝香保心丸联合单硝酸异山梨醇酯组与单用麝香保心丸或单用单硝酸异山梨醇酯组差异有统计学意义。结论麝香保心丸联合单硝酸异山梨醇酯治疗缺血性心脏病心绞痛较单用效果好。     

5—单硝酸异山梨酯治疗劳力型心绞痛

目的：比较鲁南药厂生产的５－单硝酸异山梨酯（鲁南ＩＳ－５－ＭＮ）与圣多纳药厂生产的５－单硝酸异山梨酯（圣多纳ＩＳ－５０ＭＮ）治疗劳力型心绞痛的疗效。方法：劳力型心绞痛５０例（男性３０例，女性２０例；年龄５８±ｓ６ａ）采用鲁南ＩＳ－５－ＭＮ２０￣４０ｍｇ，ｐｏ，ｔｉｄ治疗。另有劳力型心绞痛２０例（男性１２例，女性８例；年龄５９±８ａ）采用圣多纳ＩＳ－５－ＭＮ２０￣４０ｍｇ，ｐｏ，ｔｉｄ治疗。２组疗程     

5—单硝酸异山梨醇酯缓释胶囊治疗老年稳定型心绞痛临床观察

目的：了解5-单硝酸异山梨醇酯缓释胶囊对老年稳定型心绞痛的疗效。方法：56例老年稳定性心绞痛患者,采用自身对照法,共观察4周,前2周为对照期,除维持β受体阻滞剂及钙通道拮抗剂外,停用一切长效硝酸酯类药物,后2周为治疗期,加用5-单硝酸异山梨醇酯缓释胶囊40mg/qd。结果：5-单硝酸异山梨醇酯缓释胶囊缓解心绞痛的有效率为82.1%;用Holter监测,其减少心肌缺血发作的有效率为88%。结论：5-单硝酸异山梨醇酯缓释胶囊治疗老年心绞痛,具有持续作用长,副作用小,简便有效的优点。     

5－单硝酸异山梨酯片的比色测定

５－单硝酸异山梨酯片的比色测定邵文（上海延安制药厂制剂研究所，上海２０００５０）ＣＯＬＯＲＩＭＥＴＲＩＣＤＥＴＥＲＭＩＮＡＴＩＯＮＯＦＩＳＯＳＯＲＢＩＤＥ５－ＭＯＮＯＮＩＴＲＡＴＥＴＡＢＬＥＴＳ￥ＳＨＡＯＷｅｎ（ＤｉｖｉｓｉｏｎｏｆＰｈａｒｍａｃｅｕ...     

5—单硝酸异山梨酯治疗冠心病心绞痛45例

目的;观察５－硝酸异山梨酯治疗４５例冠心病心绞痛的疗效。方法：冠心病心绞痛４５例,给予５－单硝酸异山梨酯片剂口服,剂量为２０ｍｇ,Ｂｉｄ,疗程４周,观察心电图,心肌耗氧量及不良反应。结果：冠心病心绞痛患者经５－单硝酸异山梨酯治疗后,心电图,心肌耗氧量比治疗前有显著改善（Ｐ〈０．０５）,结论：５－单硝酸异山梨酯治疗冠心病心绞痛简单易行,安全可靠。     

兔血浆中5-单硝酸异山梨醇酯及药动学参数的毛细管气相色谱-电子捕获检测法测定

采用毛细管气相色谱－电子捕获检测法测定兔血浆中的5－单硝酸异山梨醇酯及其在兔体内的获物动力学参数。结果显示血浆药物浓度在50－1500ng/ml范围内线性关系良好，通过回收率试验确定了方法的准确度。     

5-单硝异山梨醇酯注射液对心力衰竭疗效及血流动力学的影响

目的：比较静脉滴注5－单硝异山梨醇酯（5－ISMN）与二硝酸异山梨醇酯（ISDN）注射液对充血性心力衰竭患者的疗效及血液动力学的影响。方法：采用随机,单盲的方法,将63例患者分成两组,分别给予5－单硝异山梨醇酯和二硝酸异山梨醇酯注射液20mg,测定两组病人用药前、后血压、心率、心功能及血液动力学指标。结果：5－单硝异山梨醇酯和二硝酸异山梨醇酯注射液显效率分别为43.75%和48.38%,总有效率分别为93.75%和96.76%,治疗后两组疗效显著,两组间无显著性差异。两药均有降低血压、心率,增加心排血量,改善心功能的作用。5－单硝异山梨醇酯治疗后,肺毛细血管楔嵌压、肺动脉平均压、右房压等指标下降。结论：5－单硝异山梨醇酯注射液与二硝酸异山梨醇酯注射液相同,对充血性心力衰竭有显著疗效。     

中国人口服5-单硝酸异山梨醇酯缓释片的药动学和不良反应探讨

目的 :研究健康中国人口服 5 单硝酸异山梨醇酯缓释片 (5 0mg)的药动学 ,并同时观察不良反应。 方法 :受试者口服单剂量 5 单硝酸异山梨醇酯缓释片 (5 0mg) ,气相色谱法测定血清中 5 单硝酸异山梨醇酯的浓度。结果 :5 单硝酸异山梨醇酯缓释片的AUC0 ∞ =(10 10 9± 16 47)ng·ml-1·h-1,Tmax=(4.7± 0 .5 )h ,Cmax=(784± 83)ng·ml-1,T1/2 =(8.4± 1.9)h ;5 单硝酸异山梨醇酯缓释片的不良反应发生率为 83.3% ,主要表现为头痛、头晕和嗜睡。结论 :中国人服用 5 单硝酸异山梨醇酯缓释片时应适当减小剂量。     

5-HT5 receptors

The 5-HT(5) receptor family consists of two members designated as 5-HT(5A) and 5-HT(5B). To date the 5-HT(5A) receptor has been identified in the mouse, rat, and human. The 5-HT(5B) receptor also is expressed in the mouse and rat, but not in the human where the coding sequence is interrupted by stop codons. Both receptors are essentially limited in distribution to the central nervous system (CNS), although the 5-HT(5A) receptor has also been found on neurons and neuronal-like cells of the carotid body. Within the CNS the 5-HT(5A) receptor shows a relatively broad distribution, while the 5-HT(5B) receptor has a very restricted distribution. The 5-HT(5A) receptor has been demonstrated to couple to G proteins, and the primary coupling appears to be through Gi/o to inhibit adenylyl cyclase activity. The 5-HT(5) receptors have not been extensively characterized pharmacologically. Both receptors show their highest affinity for LSD, which appears to act as a partial agonist at the 5-HT(5A) receptor. Amongst agonist-like molecules, 5-CT (5-carboxamidotryptamine) also has high affinity and has greater potency and affinity at the 5-HT(5A) receptor than does 5-HT itself. Both [(125)I]LSD and [(5)H]5-CT have been used as radioligands to study the receptors in vitro. Nothing is known about the role of the 5-HT(5B) receptor in vivo. A mouse line has been developed where the 5-HT(5A) receptor has been knocked out and these animals have been shown to have a diminished response to LSD-induced increases in locomotion. The 5-HT(5) receptors remain as two of the least studied and understood of the 5-HT receptor subtypes.     

5-氟胞苷和5''-脱氧-5-氟胞苷的合成

5-氟胞嘧啶经苯甲酰化保护后分别与供糖体四乙酰核糖和5-脱氧三乙酰核糖缩合,再经氨解,以45.7%和42.6%的收率分别制得5-氟胞苷和5'-脱氧-5-氟胞苷.     

5-氟胞苷和5＇-脱氧-5-氟胞苷的合成

5-氟胞嘧啶经苯甲酰化保护后分别与供糖体四乙酰核糖和5-脱氧三乙酰核糖缩合,再经氨解,以45.7%和42.6%的收率分别制得5-氟胞苷和5＇-脱氧-5-氟胞苷。     

Synthesis and biological activities of 5-trifluoromethyl-5'-azido-2',5'-dideoxyuridine and 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine.

5-Trifluoromethyl-2'-deoxyuridine (1) was tosylated with p-toluenesulfonyl chloride in dry pyridine at 3 degrees to give 5-trifluoromethyl-5'-O-(p-tolylsulfonyl)-2'-deoxyuridine (2), which was converted to 5-trifluoromethyl-5'-azido-2',5'-dideoxyuridine (3) by reacting with lithium azide in N,N-dimethylformamide at 85-90 degrees for 2 h. Compound 3 was then hydrogenated in ethanol-water (1:1, v/v) at room temperature and 35 psi of hydrogen pressure, using 10% palladium on charcoal as cstalyst, to yield 5-trifluoromethyl-5'-amino-2',5'-dideoxyuridine (4). Compound 4 is about fourfold less potent than compound 1 as an antiviral agent but is about 40-fold less toxic to the host Vero cells. Thus the therapeutic index of compound 1 has been improved by a factor of 10 by replacement of the 5'-hydroxyl with an amino group. Compound 1, however, is more than 100-fold more inhibitory to Sarcoma 180 cells in culture relative to compound 4. Compound 3 is markedly less potent than compound 1 or 4 as either an antiviral or an antineoplastic compound.     

5'-deoxy-5'-methylthioadenosine phosphorylase--IV. Biological activity of 2-fluoroadenine-substituted 5'-deoxy-5'-methylthioadenosine analogs

5'-Deoxy-5'-methylthioadenosine phosphorylase (MTAPase) phosphorolyzes 5'-deoxy-5'-methylthioadenosine (MTA) generated during polyamine biosynthesis to adenine and 5-methylthioribose-1-phosphate. Two doubly-substituted, 2-fluoroadenine-containing analogs of MTA, 5'-deoxy-2-fluoroadenosine (5'-dFAdo) and 5'-deoxy-5'-iodo-2-fluoroadenosine (5'-IFAdo), were synthesized and studied as substrates of MTAPase: their reaction with this enzyme resulted in the liberation of the cytotoxic base, 2-fluoroadenine, as well as potentially cytotoxic analogs of 5-methylribose-1-phosphate. The activities of these MTA analogs were compared to that of the singly-substituted analog, 5'-deoxy-5'-methylthio-2-fluoroadenosine (5'-MTFAdo). The cytotoxic action of these MTA analogs depended primarily on their conversion to 2-fluoroadenine-containing nucleotides, as a cell line that contains both MTAPase and adenine phosphoribosyltransferase (APRT) activity (HL-60 human promyelocytic leukemia) readily converted these MTA analogs to 2-fluoroadenine-containing nucleotides (especially 2-fluoroadenosine triphosphate) and was highly sensitive to the growth-inhibitory effects of all three compounds (IC50 values in the 10(-8) M range), whereas cell lines lacking MTAPase (CCRF-CEM human T-cell leukemia) or APRT (HL-60/aprt1 cells) did not form analog nucleotides and were relatively insensitive to these compounds (IC50 values in the 10(-5) M range). The doubly-substituted analogs were not more growth inhibitory than 5'-MTFAdo in wild type HL-60 cells as the potent effects of 2-fluoroadenine may mask the activity of the 5-methylthioribose-1-phosphate analogs generated in the reaction of these compounds with MTAPase. 5'-dFAdo and 5'-IFAdo also were irreversible inhibitors of S-adenosylhomocysteine hydrolase, which may explain in part the weak but observable growth inhibitory action of these compounds against MTAPase-deficient cell lines.