Anticonvulsant Activities of 4–Bromobenzaldehyde Semicarbazone

Summary: Some of the properties of 4–bromobenzalde-hyde semicarbazone (compound IV), a prototype molecule of a new class of anticonvulsants, aryl semicarbazones, are described. Compound IV demonstrated activity in the maximal electroshock (MES) and subcutaneous pentylenetetrazol (scPTZ) tests in mice, with low neurotoxicity. When given orally to rats, it displayed high potency in the MES test and very low neurotoxicity, resulting in a high protective index (PI). Compound IV displayed no proconvulsant properties, and development of rapid tolerance was not noted. When administered intraperitoneally (i.p.) at doses of 100, 300, or 600 mg/kg to rats, compound IV had no effect on levels of γ-aminobu-tyric acid (GABA) or on GABA-T activity in whole brain. When tested in vitro, compound IV had no effect on rat brain GABA-T at a drug concentration of 100 μM. Although the activities of certain drug-metabolizing enzymes were increased after oral administration of compound IV to rats, these effects were less prominent than those of phenytoin (PHT) and carbamazepine (CBZ). The principal mode of action of compound IV does not appear to be an interaction with the GABA_A receptor complex, and other mechanisms, involving excitatory amino acid neurotransmission, will have to be considered in future investigations of the anticonvulsant activity of this compound.     

米非司酮作用于兔输卵管收缩活动与Ca^2＋关系的研究

通过“结合化学分离与原子吸收分光光度法”对Ca^2 含量测定和离体输卵管肌条收缩记录方法，研究米非司酮（Ru486)对增加假孕（4d)兔输卵管平滑肌收缩频率，而不改变其收缩张力和振幅时与Ca^2 之间的关系，结果提示：（1）Ru486对输卵管分泌液和组织内Ca^2 的含量分布无明显影响；（2）Ru486具有降低细胞外液高Ca^2 浓度促Ca^2 内流，而使收缩增强的效应，且能协同Ca^2 通道阻断剂（Verapamil)抑制细胞外Ca^2 内流，而致收缩减弱的效应。     

905株革兰阴性杆菌对氟哌酸耐药性的观察

本文就氟哌酸广泛应用于临床后,对近三年来从各种标本中分离出的905株革兰阴性杆菌吋氟哌酸的耐药性进行了观察研究,发现其敏感率呈逐年下降趋势,敏感率依次为93.39%、85.56%、79.38%,同时耐药性逐年升高,耐药率依次为4.96%、8.45%、17.27%。     

Model Features of a Cardiac lontophoretic Drug Delivery Implant

Pharmaceutical Research -     

Two deaths from intravenous nifedipine abuse

Summary An incident is reported in which 2 intravenous drug abusers died as the result of uncontrolled experimentation with intravenous injection of the common anti-hypertensive and anti-anginal drug Nifedipine (Adalatt.m. Bayer), probably in mistake for the commonly abused short-acting benzodiazepine drug Temazepam. Large quantities of Nifedipine were identified in the blood of both deceased men by gas chromatography. Apart from intense gastric mucosal congestion, pulmonary oedema and general visceral congestion, the autopsy findings were entirely nonspecific. The similarity in colour, shape and texture between capsules of Nifedipine and those of Temazepam is likely to have prompted the mistake.     

药物不良反应国内文献题录检索系统

本文报道了药物不良反应国内文献题录检索系统的设计原理、功能特点,以输入药名及不良反应类别为例,显示了检索系统操作简便,提供信息及时准确的特点。本系统可从药名、不良反应类别及作者等多方面进行检索,可为查询者提供所需的详细资料,弥补了人工查阅文献的不足。并将继续扩大文献资料库,由题录向电报文体文摘形式转化,以贮存更多的信息。     

Effect of Omeprazole on Diazepam Disposition in the Rat: in Vitro and in Vivo Studies

Purpose. The inhibitory effects of omeprazole on diazepam metabolism in vitro and in vivo are compared in the rat. Methods. 3-hydroxylation and N-demethylation of diazepam was investigated in the presence of a range of omeprazole concentrations (2-500µM) in hepatic microsomes and hepatocytes. Zero order infusions together with matched bolus doses of omeprazole were used to achieve a range of steady state plasma concentrations (10-50mg/ L) and to study the diazepam-omeprazole interaction in vivo. Results. The 3-hydroxlation pathway was more prone to inhibition (K_Is 108 ± 30 and 28 ± 11 µM in microsomes and hepatocytes, respectively) than the demethylation pathway (K_Is of 226 ± 76 and 59 ± 27 µM in microsomes and hepatocytes, respectively). In both in vitro systems, the mechanism of inhibition was competitive with Km/K_I ratios larger than 1 for the 3HDZ pathway and smaller than 1 for the NDZ pathway. There was an omeprazole concentration dependent decrease in diazepam clearance in vivo which could be modelled using a simple inhibition equation with a K_I of 57µM (19.8mg/L). In contrast there was no statistically significant change in the steady state volume of distribution for diazepam in the presence of omeprazole. Conclusions. The in vivo K_I for the omeprazole: diazepam inhibition interaction shows closer agreement with the K_I values obtained in hepatocytes than with those observed in microsomes.     

消炎痛对大鼠肾上腺素性肺损伤的影响

本实验采用静脉注射肾上腺素造成大鼠肺损伤模型,观察消炎痛对肾上腺素性肺损伤时,肺血管壁通透性及肺组织形态学影响。结果表明:消炎痛可预防肾上腺素所致的肺血管壁、肺泡壁通透性增高(分别为P<0.025;P<0.01),延长存活时间(P<0.001);形态学检查:肺损伤明显减轻(P<0.005)。提示前列腺素(PG)参与了肾上腺素性肺损伤。     

Effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites

The effects of dextropropoxyphene on the steady-state kinetics of oxcarbazepine and its metabolites were investigated in eight patients with epilepsy or trigeminal neuralgia. One patient dropped out of the study, presumably due to side-effects of dextropropoxyphene. Dextropropoxyphene did not affect the plasma levels of the principal active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. Since dextropropoxyphene is known to increase the plasma levels of carbamazepine, leading to toxicity, the findings of this study suggest that oxcarbazepine is a useful alternative to carbamazepine when concomitant dextropropoxyphene therapy is required.