黎芦碱对分离的大鼠神经细胞内游离钙的影响

用Ｆｕｒａ－２双波长荧光法测得分离的大鼠神经细胞静息胞内游离钙浓度（［Ｃａ２＋］ｉ）为１１９．４±９．１ｎｍｏｌ·Ｌ－１（ｎ＝８）．藜芦碱（１０－４ｍｏｌ·Ｌ－１）可显著促进Ｃａ２＋内流而使［Ｃａ２＋］ｉ升高（Ｐ＜０．０１，ｎ＝８）；尼莫地平对静息［Ｃａ２＋］ｉ无影响．但能浓度依赖性地对抗藜芦碱所致［Ｃａ２＋］ｉ的升高。提示藜芦碱诱发的［Ｃａ２＋］ｉ升高由存在于神经细胞膜上的Ｌ型电压依赖性钙通道介导；尼莫地平可用以间接地保护神经细胞免受藜芦碱的兴奋毒性。     

Spinal cord injury in rats: inability of nimodipine or anti-neutrophil serum to improve spinal cord blood flow or neurologic status

The role of a calcium-mediated increase in vascular resistance and of vascular damage caused by polymorphonuclear leukocytes (PMNLs) in the development of neurologic deficit and disturbance of spinal cord circulation following spinal cord compression was studied in the rat. Spinal cord injury was induced by 5 min of compression with a load of 35 g on a 2.2 X 5.0 mm compression plate. This caused transient paraparesis. The rats received either the calcium receptor antagonist nimodipine or an anti-rat neutrophil serum (ANS). Nimodipine was infused i.v. for 4 h in an amount of 1.5 micrograms/kg/min starting 60 min after trauma. The number of circulating PMNLs was depleted by intraperitoneal injection of an ANS raised in sheep given 12 h before trauma. This caused a reduction to about 2% of the pre-ANS value. Controls received saline or normal sheep serum. The motor performance was assessed daily on the inclined plane. On day one, the day after injury, the capacity angle had decreased from about 63 degrees preoperatively to close to 32 degrees in the experimental groups. There was then a slow improvement in both the control and experimental groups and on day 4 the capacity angle was close to 43 degrees in all 3 groups. Spinal cord blood flow, as measured with the 14C-iodoantipyrine autoradiography method, was similar in all groups on day 4. As neither the neurologic dysfunction nor the spinal cord blood flow was affected by post-trauma treatment with nimodipine or pretreatment with ANS, the possibility that calcium-mediated vasoconstriction or PMNLs play a role in the development of posttraumatic neurologic disability was not supported by this study.     

尼莫地平对新生大鼠缺氧缺血性脑病的防治作用

目的与方法：采用新生大鼠缺氧缺血性脑病（HIE）模型来探讨其发病机制及尼莫地平对HIE脑损伤的防治作用。选用7d Wistar大鼠18只，随机分为伪手术组、HIE组、HIE＋尼莫地平（NM）治疗组。各组动物于实验开始后24h断头取脑组织进行病理学检查，并测定脑组织中钙、丙二醛（MDA）及水含量。结果：HIE为伪手术组相比，上述各指标值均增高（P＜0．01），脑病理改变明显，且HIE组脑钙、MDA与水含量呈显著正相关关系。与HIE组相比，尼莫地平治疗组各指标明显降低，脑病理改变明显改善。结论：HIE病生理过程与细胞内钙超载密切相关，尼莫地平对新生大鼠HIE有明显的防治作用。     

创伤性蛛网膜下腔出血与尼莫地平的治疗作用

将我科自１９９５年１０月至１９９６年６月经首次ＣＴ检查发现创伤性蛛网膜下腔出血（ｔＳＡＨ）的４３例住院病人按单、双日分为尼莫地平治疗组和对照组发现：尼莫地平能明显减少不良预后（死亡、植物生存和重残）发生率，伤后 ３月，尼莫地平组与对照组不良预后分别为 ２６％对 ４５％， Ｐ＜０． ０５。     

Calcium channel antagonists part V: Second-generation agents

Summary Second-generation agents include new dihydropyridines, such as amlodipine, felodipine, isradipine, nicardipine, nimodipine, nisoldipine, and nitrendipine. Verapamil-like agents include tiapamil, gallopamil, and anipamil. Among the diphenylalkylamines, bepridil is of special interest. New preparations of existing agents include slow-release formulations of nifedipine, verapamil, and diltiazem. From all these agents will be selected those that are longeracting and provide higher vascular selectivity.[This article appeared in Cardiovascular Drugs and Therapy, 2:191–203, 1988.]     

尼莫地平与硝苯啶治疗原发性高血压病的比较50例

原发性高血压病50例,其中采用尼莫地平治疗者25例(男24例,女1例,年龄64±5a)剂量30-60mg,tid-qid.另25例用硝苯啶对照治疗,其中男23例,女2例,年龄65±4a,剂量10-20mg,tid-qid。2组均以4wk为一个疗程。尼莫地平组总有效率92％,硝苯啶组为88％。2组自身对照t检验,P<0.01,组间比较,P>0.05。不良反应均轻微。     

尼莫地平、复方丹参对高血压性脑出血血肿吸收及神经功能的影响

目的探讨尼莫地平、复方丹参注射液对高血压性脑出血(H IH)血肿吸收及神经功能的影响。方法选择H IH发病时间24 h~3 d内无活动性出血且生命体征平稳者85例,分为两组。治疗组在常规治疗基础上头3 d内给尼莫地平20 mg,3次/d,口服或鼻饲;复方丹参10 m l加入250 m l葡萄糖液或生理盐水中静滴,每天1次,共14 d。对照组仅给常规治疗。结果治疗组临床显效率65.1%显著高于对照组的42.9%(P<0.05)。治疗组血肿吸收速度,尤其在2周后也明显快于对照组(P<0.01),但神经功能缺损评分两组无显著差异(P>0.05)。结论尼莫地平、复方丹参注射液可以促进H IH的血肿吸收、脑水肿消退及提高疗效。     

Morbidity and mortality after early aneurysm surgery — a prospective study with nimodipine prevention

Summary Based on the outcome in 116 consecutive patients who were subjected to early aneurysm operation combined with additional nimodipine treatment, and who were controlled by transcranial Doppler (TCD) sonography, a morbidity and mortality analysis was performed. Of the 84 patients who preoperatively were in Hunt & Hess grades III, 79 patients (94%) were considered to show a favourable (good-fair) late recovery, while one patient (1%) had a poor outcome, and four patients (5%) died. Of the 32 poor condition patients (H & H IV–V), 17 (53%) showed a favourable recovery, while seven (22%) had a poor outcome, and eight patients (25%) died. Altogether, 20 patients (17%) had an unfavourable (poor-dead) outcome. Only two of these patients showed delayed ischaemic deterioration, one as a consequence of a secondary occlusion of perforating branches from the basilar artery and one with decompensated vasospasm after the evacuation of an epidural haematoma and a longlasting severe systemic hypotension; both these patients died. In another six of the patients with an unfavourable outcome, this was mainly related to a complicated surgery. The unfavourable outcome was related to primary brain damage produced by the subarachnoid haemorrhage (SAH) in ten patients and in two patients to internal medical complications. In addition to the two patients who died following delayed deterioration, secondary neurological dysfunction occurred in 11 patients. In 10 of these patients transient neurological dysfunction was attributed to vasospasm or to a combination of vasospasm with intraoperative or postoperative complications. One further case of delayed deterioration was attributed to secondary occlusion of the internal carotid artery after a complicated operation. From these data we conclude that following early aneurysm operation combined with intravenous nimodipine treatment, vasospasm alone is no more a major clinical problem. Morbidity and mortality are mainly related to primary effects of the SAH and/or complicated surgery.     

尼莫地平对感染性脑水肿的脑保护作用

观察百日咳菌液诱导的感染性脑水肿不同时间大鼠脑含水量和伊文思蓝（ＥＢ）含量的变化，以及Ｎｉｍｏｄｉｐｉｎｅ对感染性脑水肿脑含水量和ＥＢ含量的影响。结果表明：感染性脑水肿在注菌后３０ｍｉｎ，脑含水量和ＥＢ含量已明显升高；应用Ｎｉｍｏｄｉｐｉｎｅ治疗后，脑组织水份含量和ＥＢ含量显著降低，脑水肿明显减轻。     

Effect of physical state and particle size distribution on dissolution enhancement of nimodipine/PEG solid dispersions prepared by melt mixing and solvent evaporation

The physical structure and polymorphism of nimodipine were studied by means of micro-Raman, WAXD, DSC, and SEM for cases of the pure drug and its solid dispersions in PEG 4000, prepared by both the hot-melt and solvent evaporation methods. The dissolution rates of nimodipine/PEG 4000 solid dispersions were also measured and discussed in terms of their physicochemical characteristics. Micro-Raman and WAXD revealed a significant amorphous portion of the drug in the samples prepared by the hot-melt method, and that saturation resulted in local crystallization of nimodipine forming, almost exclusively, modification I crystals (racemic compound). On the other hand, mainly modification II crystals (conglomerate) were observed in the solid dispersions prepared by the solvent evaporation method. However, in general, both drug forms may appear in the solid dispersions. SEM and HSM microscopy studies indicated that the drug particle size increased with drug content. The dissolution rates were substantially improved for nimodipine from its solid dispersions compared with the pure drug or physical mixtures. Among solid dispersions, those resulting from solvent coevaporation exhibited a little faster drug release at drug concentrations lower than 20 wt%. Drug amorphization is the main reason for this behavior. At higher drug content the dissolution rates became lower compared with the samples from melt, due to the drug crystallization in modification II, which results in higher crystallinity and increased particle size. Overall, the best results were found for low drug content, for which lower drug crystallinity and smaller particle size were observed.