安定对兔离体气管平滑肌收缩力的影响

为了对有气道高反应的患者选用理想的镇静安定药提供参考依据,采用研究不同浓度的安定对氯化钾、乙酰胆碱、电脉冲3种刺激因素诱发兔离体气管子滑肌收缩影响的方法。结果：0．018mmol／L的安定无明显抑制作用（P＞0．05）,0．18mmol／L和0．36mmol／L的安定可显著抑制这3种刺激因素诱发的气管平滑肌收缩（P＜0．05或P＜0．01）,β受体阻滞剂普萘乐尔和中枢性苯二氮受体阻滞剂氟马西尼不能拮抗安定对气管平滑肌收缩的抑制作用。结论：安定对兔离体气管平滑肌张力有显著的抑制作用,其部分作用机制与抑制外钙内流和内钙释放及抑制蛋白激酶C（PKC）信号传导系统有关。     

Functional and biochemical evidence for diazepam as a cyclic nucleotide phosphodiesterase type 4 inhibitor

1. The responses of the electrically-driven right ventricle strip of the guinea-pig heart to diazepam were recorded in the absence and in the presence of different selective cyclic nucleotide phosphodiesterase (PDE) inhibitors.
2. Diazepam, at concentrations ranging from 1 μM to 100 μM, was devoid of effect on the contractile force in this preparation.
3. Conversely, diazepam (5 μM–100 μM) produced a consistent positive inotropic response in the presence of a concentration (1 μM), that was without effect in the absence of diazepam, of either of the selective PDE 3 inhibitors milrinone or SK&F 94120, but not in the presence of the selective PDE 4 inhibitor rolipram.
4. This effect of diazepam was not γ-aminobutyric acid (GABA)-dependent, since it was neither mimicked nor potentiated by GABA, and was not affected by either a high concentration (5 μM) of the antagonists of the benzodiazepine/GABA/channel chloride receptor complex, picrotoxin, flumazenil and β-carboline-3-carboxylic acid methyl ester (βCCMe), or by the inverse agonists, β-carboline-3-carboxylic acid N-methylamide (βCCMa) and methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM, 0.1 μM). Furthermore, a specific antagonist of the peripheral benzodiazepine receptors, PK 11195 (5 μM), did not influence the effect of diazepam.
5. Biochemical studies with isolated PDEs, confirmed that diazepam selectively inhibits type 4 PDE from guinea-pig right ventricle rather than the other PDEs present in that tissue. The compound inhibited this enzyme in a non-competitive manner. Diazepam was also able to inhibit PDE 5, the cyclic GMP specific PDE absent from cardiac muscle, with a potency close to that shown for PDE 4.
6. Diazepam displaced the selective type 4 PDE inhibitor, rolipram from its high affinity binding site in rat brain cortex membranes, and also potentiated the rise in cyclic AMP levels induced by isoprenaline in guinea-pig eosinophils, where only type 4 PDE is present.
7. The PDE inhibitory properties of diazepam were shared, although with lower potency, by other structurally-related benzodiazepines, that also displaced [³H]-rolipram from its high affinity binding site. The order of potency found for these compounds in these assays was not related to their potencies as modulators of the GABA receptor through its benzodiazepine binding site.
8. The pharmacological and biochemical data presented in this study indicate that diazepam behaves as a selective type 4 PDE inhibitor in cardiac tissue and this effect seems neither to be mediated by the benzodiazepine/GABA/channel chloride receptor complex nor by peripheral type benzodiazepine receptors.

     

布洛芬-安定混合溶液与安定溶液直肠给药治疗小儿惊厥的比较研究

目的以安定为对照，探讨布洛芬-安定混合溶液（BU—DZP）直肠给药治疗小儿惊厥的实用价值。方法在52例儿童中对比观察直肠注入布洛芬一安定混合溶液与安定溶液的吸收速度和对脑电活动的影响，并比较两药治疗小儿惊厥的疗效。结果布洛芬一安定混合溶液与安定溶液均能从直肠迅速吸收，分别于2-6min及3-8min对脑电活动产生显著影响，明显抑制癫痫样波发放。结论布洛芬一安定混合溶液与安定溶液直肠给药，均能作为小儿惊厥抢救的有效措施。     

Systemic administration of GMP induces anxiolytic-like behavior in rats

The glutamatergic system has received considerable attention over the last few years as potential target to develop anxiolytic drugs. Guanine based purines (GBPs) play an important neurmodulatory effect in the glutamatergic system. Several studies have shown the ability of the GBPs to reduce glutamatergic activity. In the present study, we investigated the anxiolytic effect of GBPs — by Guanosina Monophosphate (GMP) administration — in rodents. Adult male Wistar rats were pretreated with GMP (10, 25, 50, 100 and 150 mg/kg: i.p.); or saline (NaCl 0.9%; i.p.) (control); or, diazepam (2 mg/kg: i.p.) (positive control). One hour after the injection, the anxiety-related behaviors for each animal was evaluated in the light/dark, elevated plus-maze, and open field tasks. Additionally, purines concentration in the cerebrospinal fluid (CSF) was verified. The administration of 25 and 50 mg/kg GMP was able to promote anxiolytic-like behavior, in the light/dark and elevated plus-maze task, similar to diazepam effect. However, no changes in the open field task, or CSF purines concentration were found for either GMP or diazepam treated animals, when compared with saline group. Thus, this study suggests that acute administration of GMP was able to decrease the levels of anxiety in classical behavioral tasks.     

斯帕丰促进产程的临床疗效观察

目的观察斯帕丰促进和加速产程的疗效以及对母婴安全的影响.方法选择正常初产妇宫口开大＞3 cm者97例随机分为斯帕丰组(51例)和安定组(46例),分别予以斯帕丰40 mg及安定10 mg静脉推注,观察各组的产程进展情况、对宫颈的作用及其对母婴安全的影响.结果斯帕丰组活跃期平均时间为(3.14±0.27)h,安定组为(3.85±0.27)h,斯帕丰组短于安定组,有显著性差异(P＜0.05);用药后2 h较用药前平均宫口开大斯帕丰组为(4.38±0.22)cm,安定组(2.67±0.12)cm,有显著性差异(P＜0.05);产程中静脉应用安定,新生儿窒息率高于静脉应用斯帕丰,斯帕丰无明显的母婴副作用.结论斯帕丰对促进宫口扩张效果优于安定,能有效地促进产程,同时对母儿无不良影响,有很好的临床应用前景.     

Caring for patients with rabies in developing countries – the neglected importance of palliative care

Although limited publications address clinical management of symptomatic patients with rabies in intensive care units, the overwhelming majority of human rabies cases occur in the rural setting of developing countries where healthcare workers are few, lack training and drugs. Based on our experience, we suggest how clinicians in resource‐limited settings can make best use of essential drugs to provide assistance to patients with rabies and their families, at no risk to themselves. Comprehensive and compassionate patient management of furious rabies should aim to alleviate thirst, anxiety and epileptic fits using infusions, diazepam or midazolam and antipyretic drugs via intravenous or intrarectal routes. Although the patient is dying, respiratory failure must be avoided especially if the family, after being informed, wish to take the patient home alive for funereal rites to be observed. Healthcare staff should be trained and clinical guidelines should be updated to include palliative care for rabies in endemic countries.     

Lorazepam and diazepam rapidly relieve catatonic signs in patients with schizophrenia

The uses of lorazepam and electroconvulsive therapy (ECT) have been proven to be effective in treating catatonia. In the present study a modified treatment strategy (i.e. lorazepam i.m. injection or diazepam infused i.v. if lorazepam failed, not with ECT) was proposed to rapidly relieve catatonic signs in patients with schizophrenia. During a 3-year period, 14 patients with catatonic schizophrenia in Chinese ethnic background Taiwanese were brought to the emergency unit of a general hospital. First, the patients were immediately treated with lorazepam 1 or 2 ampules (2 mg/mL per ampule) i.m. injection (IMI) during 2 h. Second, if the previous 2 ampules of lorazepam IMI failed, diazepam infused i.v. (10 mg/2 mL per ampule) in normal saline 500 mL every 8 h would be done during 1 day. The response rate of catatonic signs in these 14 patients with lorazepam IMI during the first 2 h was 85.7% (12/14). However, according to the results of this method, the total response rate to benzodiazepines during 1 day was 100%(14/14). These results suggested that this modified treatment strategy could rapidly and completely relieve catatonic signs, even without the use of ECT.     

Visualization of alpha5 subunit of GABAA/benzodiazepine receptor by 11C Ro15-4513 using positron emission tomography

Although [(11)C]Ro15-4513 and [(11)C]flumazenil both bind to the central benzodiazepine (BZ) receptors, the distributions of the two ligands are not identical in vivo. Moreover, the in vivo pharmacological properties of [(11)C]Ro15-4513 have not been thoroughly examined. In the present study, we examined the pharmacological profile of [(11)C]Ro15-4513 binding in the monkey brain using positron emission tomography (PET). [(11)C]Ro15-4513 showed relatively high accumulation in the anterior cingulate cortex, hippocampus, and insular cortex, with the lowest uptake being observed in the pons. Accumulation in the cerebral cortex was significantly diminished by the BZ antagonist flumazenil (0.1 mg/kg, i.v.), but not that in the pons. Using the pons as a reference region, the specific binding of [(11)C]Ro15-4513 in most of the cerebral cortex including the limbic regions clearly revealed two different affinity sites. On the other hand, specific binding in the occipital cortex and cerebellum showed only a low affinity site. Zolpidem with affinity for alpha1, alpha2, and alpha3 subunits of GABA(A)/BZ receptor fully inhibited [(11)C]Ro15-4513 binding in the occipital cortex and cerebellum, while only about 23% of the binding was blocked in the anterior cingulate cortex. Diazepam with affinity for alpha1, alpha2, alpha3, and alpha5 subunits inhibited the binding in all brain regions. Since Ro15-4513 has relatively high affinity for the alpha5 subunit in vitro, these in vivo bindings of [(11)C]Ro15-4513 can be interpreted as the relatively high accumulation in the fronto-temporal limbic regions representing binding to the GABA(A)/BZ receptor alpha5 subunit.     

Comparison of Paracetamol and Aminophenazone Plus Diazepam Suppositories for Anxiety and Pain Relief after Tonsillectomy in Children

The anxiety and pain-relieving effect of paracetamol 10 mg/kg or a combination of aminophenazone 4 mg/kg and diazepam 0.2 mg/kg suppositories was studied in 82 children after tonsillectomy in a double-blind study. Both suppositories were studied after halothane or enflurane anaesthesia. At 30 min after administration of coded suppositories, 88-90% of the children in various groups needed extra analgesics, and received pethidine 0.5 mg/kg i.v. Thereafter, the anxiety and pain relief was satisfactory in all groups. There was no significant difference between the effects caused by the drugs. No bleeding occurred from the operation site in any of the study groups. The results suggest that both paracetamol and a combination of aminophenazone and diazepam in the doses used here were weak analgesics for throat pain after tonsillectomy in children during the early postoperative period.