Nimodipine对脑外伤后脑水及脑皮质和血清钙含量的影响

本文观察了脑损伤后不同时间大鼠脑水含量和脑皮质及血清钙含量变化,以及Nimodipine对外伤性脑水肿和钙含量变化的影响。结果表明,脑损伤后6h脑白质水含量巳明显增多,为79.87±0.58(P<0.01),伤后48h达峰值,为81.02±0.51:脑皮质水含量稍有增加。脑皮质及血清钙含量均有不同程度升高,以脑皮质升高较为明显,伤后48h高达24.12±10.22mmol/kg干脑,为对照值的1.8倍.应用Nimodipine治疗,可显著降低脑皮质钙含量,伤后立即接受治疗组为16.78±4.98mmol/kg干脑(P<0.05),脑水肿明显减轻,为78.98±0.89(P<0.01)。

新型钙拮抗剂Nimodipine的质谱研究

本文报告了新型钙拮抗剂Nimodipine的EIMS谱、HR -EIMS数据和1 3 CNMR(COM .INEPT)谱和数据。根据HREI数据讨论了主要特征碎片离子的可能裂解途径。其中许多碎片离子是由麦氏重排而得。

Lamotrigine联合钙通道阻滞剂Nimodipine治疗局灶性脑缺血的实验研究

目的:观察同时应用钠通道阻滞剂和钙通道阻滞剂对鼠局灶性脑缺血的保护作用。方法:采用单尼龙线线栓法制备鼠大脑中动脉缺血3小时再灌流21小时模型,分别观察lamotrigine(20mg/kg ip),nimodipine(1μg/kg/min iv)以及两者联合应用对在鼠神经功能缺损的恢复、梗塞体积、突触体内游离钙浓度的影响。结果:联合应用lamotrigine和nimodipine缩小大鼠梗塞体积,恢复神经功能缺损较单独应用lamotrigine或nimodipine效果更明显(P<0.05)。结论:联合使用钠通道阻滞阻滞剂和钙通道阻滞剂优于单用其中一种药。

Hot spots and future directions of research on the neuroprotective effects of nimodipine

Calcium antagonists are widely used in the clinical treatment of ischemic cerebrovascular disease because of their vascular and neuroprotective effects. Nimodipine, a typical calcium antagonist, can cross the blood-brain barrier and act selectively at neurons and blood vessels of target tis-sues, thus exerting neuroprotective effects. The aim of the present study was to explore the hot spots and future trends of research on the neuroprotective effects of nimodipine. We retrieved 425 articles on the neuroprotective effects of nimodipine that were indexed in the Web of the Science database between 2000 and 2014. The retrieved articles were analyzed using document analysis reporting and the derived information function in the Web of Science, and the infor-mation visualization software CiteSpace III. The reference co-citation network was plotted, and the high frequency key words in these publications were used to analyze the research fronts and development trends for nimodipine neuroprotection. According to these co-citation clusters, the research front of nimodipine neuroprotection is the use of randomized controlled trials to study nimodipine intervention of subarachnoid hemorrhage. Using time zone view analysis on hot spots labeled with a key word, the areas of interest in the ifeld of nimodipine neuroprotection are nimodipine pharmacology and therapeutics, blood-brain barrier, trials, and anti-angiospasm.

Nimodipine for treatment of perifocal edema following aspiration and drainage in patients with cerebral hemorrhage

BACKGROUND： After cephalophyma removal, perifocal edema does not disappear subsequently, but progresses occasionally. Nimodipine can improve cerebral blood flow, so it maybe reduce cerebral edema area, and speed up the absorption of edematous fluid. OBJECTIVE： To observe the effect of nimodipine on perifocal edema area and neurologic function in patients with hypertensive intracerebral hemorrhage （HICH） following stereotaxic aspiration. DESIGN： Clinical controlled observation. SETTING： Department of Neurology, Third Hospital Affiliated to Liaoning Medical University. PARTICIPANTS： Totally 116 HICH inpatients admitted to the Department of Neurology, Third Hospital Affiliated to Liaoning Medical University from January 2003 to January 2005 were involved in this experiment. They all met the classification and diagnosis of cerebrovascular disease proposed in 1995 4th National Conference on Cerebrovascular Disease. The bleeding volume ≥ 35 mL was confirmed by skull CT. The involved patients, 64 male and 52 femlae, averaged 63 years old, ranging from 40 to 70 years. All the patients suffered from unilateral cerebral hemisphere hemorrhage, and muscle strength of paralyzed limb was less than degree Ⅲ. Informed consents of therapeutic items were obtained from all the patients and relatives. METHODS： ① According to different wills, the patients were assigned into treatment group （n =60） and control group （n =56）. In the treatment group, the involved patients, 32 male, 28 female, averaged 63 years. They underwent operation and administration of nimodipine. In the control group, the involved patients, 30 male and 26 female, averaged 62 years old. They all underwent operation simply. Patients in the two groups all received stereotaxic aspiration, drainage, dehydration, haemostasis, antiinflammation, blood pressure controlling and other treatments. Patients in the treatment group were also intravenously injected with 0.2 g/L nimodipine（Bayer Medicine Health Care Co., Ltd., Lot No. 021127） at 10 mg/d. One course of treatment was 15 days. ② According to the clinical neurologic function deficit score of stroke proposed in the 4th National Conference on Cerebrovascular Disease （mild： 0-15 points; moderate： 16-30 points; severe： 31-45 points）, neurologic function deficit score and the largest perifocal edema area of patients in two groups were recorded on the 1st, 7th and 15th days after operation. The differences in perifocal edema area and neurologic deficit score between on the 1st and 7th days and between on the 7th and 15th days were calculated. MAIN OUTCOME MEASURES： Changes in the neurologic function deficit score and the largest perifocal edema area. RESULTS： Two of treatment group and 16 of control group died. Finally, 98 patients participated in the final analysis. ①In the treatment group, the difference in the largest perifocal edema area on the postoperative 7th and 15th days and on the 1st day was （1.02±0.07） and （1.86±0.10） cm2, respectively, which changed more significantly as compared with control group, respectively [（0.02±0.04）,（0.61±0.09） cm2,P 〈 0.01]. ② The difference in neurologic function deficit score between on the postoperative 15th and 1st days in the treatment group was larger than that in the control group [（7.23±0.22）,（2.68±0.32） points,P 〈 0.01]. CONCLUSION： Nimodipine obviously reduces perifocal edema area of patients with cerebral hemorrhage following aspiration and drainage, and promotes the recovery of neurologic function.

Nimodipine Modulates Bcl-2 and Bax mRNA Expression after Cerebral Ischemia

In order to explore whether the member of Bcl-2 gene family, for example, Bcl-2 and Bax, are induced after cerebral ischemia, and whether expression of genes can be modulated by calcium-antagonist, the rat cerebral ischemic models were made by occluding left middle cerebral artery. The expression of Bcl-2 and Bax mRNA was measured by RT-PCR method. After middle cerebral artery occlusion (MCAO), the expression of both Bcl-2 and Bax mRNA were induced. Level of Bcl-2 mRNA increased steadily and level of Bax mRNA increased gradually at first, reached a peak after 24 h, then decreased slowly. After administration of nimodipine, Bcl-2 mRNA was up-regulated in the hippocampus 6 and 24h after ischemia, while Bax mRNA was down-regulated 6 and 24 h after ischemia. Focal cerebral ischemia can induce proto-oncogenes to express, which was associated with apoptosis. Calcium-antagonist can up-regulate Bcl-2 mRNA and down-regulate Bax mRNA. The increased ratio of Bcl-2 and Bax mRNA may contribute to the anti-apoptic effect of nimodipine. The study indicates that pharmacological modulation of Bcl-2 family member expression could become a new strategy to manage neuronal damage.

EFFECTS OF NIMODIPINE ON PLATELET AGGREGATION AND THE ACTIVITY OF ENZYMES IN ARACHIDONIC ACID METABOLISM

The effects of nimodipine on platelet aggregation and arachidonic acid(AA)metabolism were studied in order to explore its effect on patients with thrombosis or cardiovas- cular disease.The results indicate that nimodipine(50-350μmol/L)significantly inhibits platelet aggregation induced by ADP,AA,and ionophore A23187 in a dose dependent manner.The inhibitory effects induced by ionophore A23187 could be partially antagonized by calcium(1 mmol/L).When the substrate was AA and the enzyme was supplied by pig lung microsomes,nimodipine(50-400μmol/L)significantly reduced the generation of TXB_2 and 6-keto-PGF_(1a) in parallel.When the substrate was prostaglandin endoperoxide, however,the levels of TXB_2 and 6-keto-PGF_(1a)were not significantly altered in the same concentration range.The results suggest that nimodipine is a cyclooxygenase inhibitor,and its ability to inhibit platelet aggregation is related to its calcium blocking effect.

Influences of Chloropazine, Nimodipine and Their Combination on the Toxic Effects of Cadmium in Liver and Kidney of Mice

The influences of the calmodulin antagonist chlorpromazine (CPZ), and calcium channel blocker nimodipine (NIMO) and their combination on cadmium (Cd) poisoning of mice were studied. A seties of biochemical parameters including urinary enzyme activities, blood and urine Cd levels, metallothionein (MT) contents in liver and kidney, hepatic ultrastructure and Ca2+ -Mg2+ AT-Pase activity in erythrocyte membrane were determined. Animal models for Cd poisoning were established by peritoneal injection of 1/5 LD50 CdCl2. The experimental groups were protected by administration of CPZ, NIMO and CPZ and NIMO in combination l h before the injection of CdCl2. Five days later, samples were collected for analysis. The data showed that Crs could protect kidney tissue against Cd-induced damage, as the urinary γ-glutamyl traspepti dase (γ- GT ) and N- acetyl-β-D-glucosaminidase (NAG) activities were reduced significantly. There was neither evidence of the protective effect of NIMO on kidney tissue nor an indication of a synergistic effecf of Crs and NIMO.Both CPZ and NIMO showed a considerable protective effect against the deerease in Ca2+ -Mg2+ AT-Pase activity, and a synergistic action was observed. Cd content in blood was reduced significanily by CPZ or the combination of CPZ and NIMO, but elevated by NIMO. Both CPZ and NIMO consideraby increased MT contents in livers and kidneys and ameliorated damaged to the hepatic ultrastructures caused by Cd. The results indicated that these inhibitors could protect mice against the toxic effects of Cd in liver and kidney tissues, while CPZ was more efficient than NIMO. The combination of CPZ and NIMO exerted a synergistic action. The protective action of these two drugs might be relevent to the function of MT.

Cooperative effect of polyvinylpyrrolidone and HPMC E5 on dissolution and bioavailability of nimodipine solid dispersions and tablets

Solid dispersion(SD)systems have been extensively used to increase the dissolution and bioavailability of poorly water-soluble drugs.To circumvent the limitations of polyvinylpyrrolidone(PVP)dispersions,HPMC E5 was applied in the formulation process and scaling-up techniques,simultaneously.In this study,SD of nimodipine(NMP)and corresponding tablets were prepared through solvent method and fluid bed granulating one step technique,respectively.Discriminatory dissolution media were used to obtain reliable dissolution results.Meanwhile,the stability study of SDs was investigated with storage under high temperature and humidity conditions.Moreover,the solubility of SDs was measured to explore the effect of carriers.The preparations were characterized by DSC,PXRD,and FTIR.Dramatical improvements in the dissolution rate of NMP were achieved by the ingenious combination of the two polymers.Binary NMP/PVP/HPMC-SDs released steadily,while the dissolution of single NMP/PVP-SDs decreased rapidly in water.The fluid-bed tablets(FB-T)possessed a similar dissolution behavior to the commercial Nimotop TM tablets.The characterization patterns implied that NMP existed in an amorphous state in our SDs.Furthermore,the results of stability tests suggested a better stability of the binary SDs.A special cooperative effect of PVP and HPMC was discovered on dissolution characteristics of NMP SDs and tablets,which could be extended to other drugs henceforth.Finally,the bioavailability of FB-T was evaluated in beagle dogs with Nimotop TM as the reference,and the results showed a higher AUC 0–12h value for FB-T.

Hypertensive-Nimodipine Therapy for Middle Cerebral Artery Vasospasm after Resection of Glioblastoma Multiforme: A Case Report and Literature Review

Delayed cerebral ischemia (DCI) due to post-brain tumor resection vasospasm is an often unrecognized yet debilitating complication. We present a patient with DCI after the resection of glioblastoma multiforme (GBM). To our knowledge, this is the first report on DCI after GBM resection. A 52-year-old female patient with headache for one month underwent subtotal resection of a left temporal GBM encasing the proximal middle cerebral artery (MCA). She was well during the immediate postoperative period but developed right upper limb dense monoparesis on postoperative day four with computed tomographic angiography confirming left MCA vasospasm. Symptoms were significantly alleviated with weeklong hypertensive therapy and nimodipine administration;however they recurred soon after cessation of treatment. A high index of clinical suspicion is needed for the diagnosis of post-tumor resection DCI. Any new postoperative neurological deficit that cannot be explained by hemorrhage, seizures or infection should be expeditiously investigated by angiography or transcranial Doppler sonography. Prompt initiation of hypertensive and nimodipine therapy can possibly reverse neurological deficit. Treatment should be guided by Doppler, angiographic or perfusion imaging studies and not by clinical improvement alone.

Solid dispersion in the development of a nimodipine delayed-release tablet formulation

Nimodipine(NMD)is a dihydropyridine calcium channel blocker with selectivity for cerebral blood vessels and the major therapeutic indication of NMD is for the prevention and treatment of delayed ischemic neurological disorders and other cerebrovascular disorders,such as stroke which is associated with biological rhythm.This study was mainly designed to solve the drawback of conventional NMD solid dosage form,low bioavailability and limited clinical efficacy,by preparing enteric solid dispersion(SD)and the SD was prepared via melting method.The physical state of the dispersed NMD in the polymer matrix was characterized by differential scanning calorimetry(DSC),powder X-ray diffraction(PXRD)and dissolution studies.Compared with pure drug and physical mixture,the dissolution of NMD-SD was enhanced dramatically(about 80%).Furthermore,in consideration of the biological rhythm of stroke,we first obtained a delayed-release tablet containing NMD-SD by a direct powder compression method.As shown in the dissolution studies,the tablet released less than 10%in the artificial gastric acid in the initial 2 h and released 32.1%,75%,more than 90%at 4,10 and 14 h respectively in the artificial intestinal fluid.This investigation has solved the problems of oral solid dosage forms of NMD,and it has the good industry prospect.

Effects of glutamate and nimodipine on survival rate of embryonic rat neuronal stem cells cultured in vitro

BACKGROUND： At least three types of calcium ion channel （T, N, and L） have been recognized in nerve ceils, but only the L type of channel is sensitive to drugs. Theoretically, nimodipine can lead to L-type channel inactivation and prevent calcium ion inflow, thereby exhibiting protective effects on nerve cells. OBJECTIVE： To observe the protective effects of nimodipine on glutamate-induced injury to embryonic rat neural stem cells, and to make a comparison with MK-801, a nonselective glutamate receptor antagonist. DESIGN, TIME AND SETTING： The present in vitro experiment pertaining to neural stem cells was performed at the Department of Neurology, First Hospital, Jilin University between January 2005 and December 2006. MATERIALS： Glutamate was sourced from the Shanghai Biological Research Institute of the Chinese Academy of Sciences. Nimodipine was provided by Bayer Company, Germany. Brain tissue was taken from Wistar rats on day 15 of gestation for isolation and culture of neural stem cells. METHODS： Passage 2 neural stem cell spheres were taken for preparation of single cell suspension. The prepared single cell suspension was divided into 4 groups： （1） Normal control, normally cultured. （2） Glutamate, cultured with 50, 100, 200, 500, and 1 000 μmol/L glutamate. （3） Nimodipine, received a 30- minute nimodipine [1×（10^-8-10^-2） g/L] culture followed by a glutamate （200 μmol/L） treatment step. （4） MK-801, given as 30- minute MK-801 （100 μmol/L） culture, followed by a glutamate （200 μmol/L） treatment step. MAIN OUTCOME MEASURES： Determination of glutamate-induced cell death by methyl thiazolyl tetrazolium （MTT） assay; calculation of neural stem cell survival rate following addition of nimodipine. RESULTS： The survival rate of neural stem cells was approximately 25.26% following 24 hour 50 μmol/L glutamate culture and gradually decreased as the glutamate dose increased （P 〈 0.05 0.01）. Only 9.27% of neural stem cells survived when the glutamate dose was 1000 μmol/L. The survival rate of neural stern cells was significantly higher, in a dose-dependent manner, in the nimodipine [1×（10^-7-10^-2） g/L] group than in the glutamate group. In addition, the MK-801 group exhibited a higher survival rate after 24 hour treatment than the glutamate group （P 〈 0.01）. CONCLUSION： Glutamate （50-1 000 μmol/L） induces injury to neural stem cells dose-dependently. Nimodipine exhibits protective effects on injury to neural stem cells and presents the effects in a dose-dependent manner at 1 ×（10^-7-10^-2） g/L. Nimodipine displays neuroprotective effects equivalent to MK-801.

Effects of calcium antagonist nimodipine on patients with severe craniocerebral trauma

The authors report the effects of a calcium antagonist, nimodipine, on severe craniocerebral trauma.A total of 488 cases of severe craniocerebral trauma with Glasgow Coma Scale (GCS) 3～8 score were recruited into the clinical study. The patients were divi

Preparation and Characterization of Nimodipine-loaded Methoxy Poly(ethylene glycol)-poly(lactic acid) Diblock Copolymer Nanoparticles

Amphiphilic diblock copolymers, methoxy poly （ ethylene glycol）-poly（lactic acid） （MePEG-PLA）, were synthesized from monomers of DL-lactide and methoxy poly （ethylene glycol） by a ring opening bulk polymerizatiou in the presence of stannous octoate. Their chemical structure and physical properties were investigated using FTIR, NMR, GPC, and fluorescence spectroscopy. To estimate the feasibility as colloidal drug carrier, nimodipine （ND） was loaded into MePEG-PLA block copolymer nanoparticles by phaseseparation/dialysis method. The mean diameter and drug loading efficiency of ND-loaded MePEG-PLA copolymer nanoparticles depended ou PLA/MePEG block composition of the copolymer and drug/polymer feed ratio in preparatiou. NMR study confirmed that nimodipine was entrapped into the hydrophobic inner core of MePEG-PLA copolymer nanoparticles and hydrophilic PEG chains were located ou the surface of the drug-loaded polymer nanoparticles. In vitro release experiments exhibited the sustained release behavior of nimodipine from MePEG-PLA copolymer nanoparticles, without any burst effect.

Bioavailability study of nimodipine in rabbit subarachnoid hemorrhage

Objective:To observe the bioavailability of subcutaneous injection of nimodipine and oral administration of nimodipine in healthy rabbits and rabbits with subarachnoid hemorrhage (SAH), and determine whether subcutaneous administration is superior to oral administration and to reach the target serum concentration.Methods: Thirty six adult male New Zealand white (NZW) rabbits were divided into 6 groups (n=6) by random number table method, including the oral nimodipine group (5 mg and 15 mg/kg,n=12), the subcutaneous injection of nimodipine group (2.5 mg, 5 mg and 15 mg/kg,n=18), SAH+ subcutaneous injection of nimodipine group (2.5 mg/kg,n=6), plasma concentrations of nimodipine in each group were measured and statistical analysis was performed.Results: (1) Oral administration of 15 mg/kg of nimodipine produced a higher Tmax and increased Cmax, which was also greater than 5 mg/kg. The time to peak plasma concentration (Tmax) observed after subcutaneous administration had an opposite trend, with 15 mg/kg resulting in a lower Tmax and a lower AUC tendency than 5 mg/kg. (2) Compared with oral administration, the average concentration of nimodipine in the subcutaneous group was significantly greater than 7 ng/mL (P<0.01), and the plasma concentration of nimodipine remained above 7 ng/mL for significantly longer than oral administration (P<0.01). (3) The Cmax, Tmax and AUC values of nimodipine in healthy NZW rabbits were not significantly different from those measured by subcutaneous injection of 5 and 15 mg/kg (P>0.05). There was no significant difference between healthy NZW rabbits [(12.9±10.0) ng/mL) and SAH [(11.8±4.6) ng/mL] NZW rabbits at the target level of treatment with an average nimodipine concentration of 7 ng/mL measured at 24 h (P>0.05).Conclusion: Subcutaneous administration of nimodipine is superior to oral nimodipine and can maintain the plasma level of nimodipine at 7 ng/mL after 24 h, which can help to study the mechanism of nimodipine in delaying vasospasm after SAH treatment.

Nimodipine对冷冻伤性脑水肿的脑保护作用

本文观察了冷冻伤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,脑含水量与EB含量之间的关系;以及尼莫地平(Nimodipine,Nim)对冷冻伤性脑水肿脑含水量和EB含量的影响。结果表明:冷冻伤脑含水量和EB含量明显升高,应用Nim治疗后,脑组织水分含量和EB含量明显降低,脑水肿减轻。这为临床颅脑损伤应用Nim治疗提供理论依据。

HPLC determination of Nimodipine in plasma with an improved sample refining method and its application in pharmacokinetic studies

In order to prepare samples for HPLC analysis with maximum drug recovery and impurity elimination, a revised method for the extraction and purification of a target substance from plasma was developed and applied in a pharmacokinetic study with Nimodipine as a model drug. After protein precipitation of a plasma sample using pure methanol and evaporation of the supernatant to dryness, methanol of various concentrations from 10% to 100% were used to dissolve the remaining residues with the goal of maximizing drug recovery and impurity elimination. Through rigorous screening with HPLC peaks from residual impurity and recovered drug as the criteria, a methanol concentration of 30% was chosen. The standard curve was linear （r2〉 0.999） over the range of 2-160 ng/mL with a limit of quantification （LOQ） of 2 ng/mL. Intra- and inter-day precision values were below 15%, and the accuracy ranged from -1.70% to 5.88% at all three quality control （QC） levels. The wavelength of maximum absorption was 238 nm, and a smaller LOQ value of 2 ng/mL was achieved compared with the reported method. The revised method was successfully applied in a pharmacokinetic study of Nimodipine in rats and sample preparations of lidocaine hydrochloride.

The efficacy and safety of nimodipine in acute ischemic stroke patients with mild cognitive impairment: a double-blind, randomized,placebo-controlled trial

Nimodipine might be effective in subcortical vascular dementia(VaD). Its benefit in preventing further cognitive decline in patients with acute ischemic stroke(AIS) and vascular mild cognitive impairment(VaMCI) remains to be established. In this multicenter, double-blind trial, we randomly assigned 654 eligible patients to nimodipine 30 mg three times a day or placebo. The primary outcome was any cognitive decline defined by the changes on the Mini-Mental State Examination(DMMSE à3) or vascular AD assessment scale cognitive subscale(DADAS-cog ! 4) at 6 months. Secondary outcomes included any distribution shift of DADAS-cog, DMMSE or cognitive improvement defined by DADAS-cog à2, or DMMSE ! 0. The primary outcome in the nimodipine group and placebo group were similar for DMMSE à3(4.18% and 7.22%, respectively, P = 0.15) and DADAS-cog ! 4(8.36% and 8.93% respectively,P = 0.88). The distribution shift of DADAS-cog and DMMSE differed significantly between the two groups(P = 0.03 and P = 0.05 respectively). Cognitive improvement occurred in 55.4% in the nimodipine group and 43.6% in the placebo group measured by DADAS-cog à2(Odds Ratio, 1.54; 95% confidence interval[CI] 1.10–2.14, P < 0.01) or 84.0% and 74.6% respectively by DMMSE ! 0(Odds Ratio, 1.79; 95% CI 1.18–2.70, P < 0.01). Nimodipine was associated with better cognitive function in the memory domain. The adverse events rate was similar in two groups. This study is registered with ClinicalTrials.gov,NCT01220622. Nimodipine did not show benefit to prevent cognitive decline in AIS patients with VaMCI, but improved cognition moderately, especially measured in the memory domain.

Effects of nimodipine and fructose-1,6-diphosphate on cerebral damage in carbon monoxide poisoning mice

Objective To study the dose- and time- dependent protective effects and the synergistic effects of nimodipine (NMDP) and fructose-1,6-diphosphate (FDP) against cerebral damage induced by acute carbon monoxide (CO) poisoning in mice. Methods Male mice were exposed to CO 170 mL/kg, i.p. After CO intraperitonealy exposure, mortality of mice, change in memory function estimated by passive avoidance test, the pathomorphologic observation of brain tissue slices, as well as changes of activities of monoamine oxidase (MAO)-B and Ca 2+-Mg 2+-ATPase in cerebral tissue were studied. In dose-dependent protective effect study, NMDP (10.6, 5.3, 2.7 mg/kg) and FDP (2.6, 1.3, 0.67 g/kg) was injected ip, respectively 15 min after CO exposure. To study the time-effect relationship of drugs, NMDP (5.3 mg/kg) and FDP (1.3 g/kg) were administered ip respectively 15 minutes, 45 minutes and 120 minutes after CO exposure. The combination of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) was administered ip15 minutes, 45 min and 120 minutes after CO exposure to study the synergism of the two drugs. Results Either NMDP (10.6, 5.3 mg/kg) or FDP (2.6, 1.3 g/kg) administered ip within 15 minutes after CO exposure significantly decreased the impairment of memory function and mortality rate induced by CO, inhibited the decrease of Ca 2+-Mg 2+-ATPase activity, blunted the rising of MAO-B activity and prevented the delayed hippocampal neuronal death in poisoning mice. To our surprise, the combined use of NMDP (2.7 mg/kg) and FDP (0.67 g/kg) within 15 minutes after CO exposure had similar effects to that in NMDP (10.6, 5.3 mg/kg) and FDP (2.6, 1.3 g/kg). Conclusions These results suggest that the impairment of CO on brain can be attenuated if NMDP or FDP are administered sufficiently and quickly as soon as possible after CO exposure and there exists a synergism of FDP and NMDP against CO poisoning damage.

Clinical Effects of Acupuncture Combined with Nimodipine for Treatment of Vascular Dementia in 30 Cases

To study the therapeutic effects of acupuncture combined with nimodipine for vascular dementia. Methods： Acupuncture was applied at Baihui （GV 20）, Shenshu （BL 23）, Geshu （BL 17）, and the points selected according to the midnight-noon, ebb-flow eight methods of the intelligent turtle, combined with the drug nimodipine. The treatment was continued for 8 consecutive weeks. Results： Of the 30 cases treated, 6 cases were cured, 21 cases improved, and 3 cases failed, with a total effective rate of 90%. Conclusion： Acupuncture at Baihui （GV 20）, Shenshu （BL 23）, Geshu （BL 17）, and the points selected according to the midnight-noon, ebb-flow eight methods of the intelligent turtle combined with the drug nimodipine can yield definite therapeutic effects for vascular dementia.