薄层扫描法测定血浆中盐酸氟桂利嗪浓度及药物动力学

血浆中盐酸氟桂利嗪经硼酸缓冲液酸化后，正戊烷－异丙醇（９８：２）提取其原型，加酸使成盐溶于无机相中，再加碱后用二氯甲烷提取，样品点于硅胶ＧＦ２５４薄层板上，以环己烷－丙酮－氯仿（９：３：５）为展开剂。氟桂利嗪在２５４ｎｍ紫外灯下呈紫色斑点，Ｒｆ＝０．５４，于ＣＳ－９３０薄层扫描仪上测定，λｓ＝２１５ｎｍ、λｇ＝３１０ｎｍ，线性范围０．３￣８μｇ，平均回收率９０．０２％。用此法测定了氟桂利嗪血药浓度     

Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons

Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.     

Effect of KB-2796, a new diphenylpiperazine Ca antagonist, on voltage-dependent Ca currents and oxidative metabolism in dissociated mammalian CNS neurons

The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA I_Ca in a concentration-dependent manner with a threshold concentration of 10⁻⁷ M when the LVA I_Ca was elicited every 30 s in the external solution with 10 mM Ca²⁺. The concentration for half-maximum inhibition (IC₅₀) was 1.9 × 10⁻⁶M. At 10⁻⁵ M or more of KB-2796, a complete suppression of the LVA I_Ca was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca²⁺ channel for LVA I_Ca voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca²⁺ channel. KB-2796 at a concentration of3.0 × 10⁻⁶M also decreased the peak amplitude of the HVA I_Ca without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10⁻⁶M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca²⁺ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage.     

三例儿童交替性偏瘫的回顾性分析

目的探讨儿童交替性偏瘫病因、临床特点、治疗效果。方法回顾性分析3例儿童交替性偏瘫患者的病因、临床表现及疗效。结果本组3例患者起病年龄均小于18个月,反复发作的交替性偏瘫；进行性的智能障碍,其中1例伴有短暂眼球震颤及眼球活动障碍,1例伴有张力障碍性姿势异常；睡眠可缓解无力及锥体外系症状,应用氟桂嗪治疗后,2例患者发作频率及持续时间降低,1例无效。结论本病病因不明,多为散发,临床表现为18月内起病的发作性交替性偏瘫,辅助检查无特征性改变,氟桂利嗪治疗部分有效。     

Effect of nilvadipine on the voltage-dependent Ca channels in rat hippocampal CA1 pyramidal neurons

Effects of nilvadipine on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) were compared with other organic Ca²⁺ antagonists in acutely dissociated rat hippocampal CA1 pyramidal neurons. The inhibitory effects of nilvadipine, amlodipine and flunarizine on LVA I_Ca were concentration- and use-dependent. The apparent half-maximum inhibitory concentrations (IC₅₀s) at every 1- and 30-s stimulation were 6.3×10⁻⁷ M and 1.8×10⁻⁶ M for flunarizine, 1.9×10⁻⁶ M and 7.6×10⁻⁶ M for nilvadipine, and 4.0×10⁻⁶ M and 8.0×10⁻⁶ M for amlodipine, respectively. Thus, the strength of the use-dependence was in the sequence of nilvadipine>flunarizine>amlodipine. Nilvadipine also inhibited the HVA I_Ca in a concentration-dependent manner with an IC₅₀ of 1.5×10⁻⁷ M. The hippocampal CA1 neurons were observed to have five pharmacologically distinct HVA Ca²⁺ channel subtypes consisting of L-, N-, P-, Q- and R-types. Nilvadipine selectively inhibited the L-type Ca²⁺ channel current which comprised 34% of the total HVA I_Ca. On the other hand, amlodipine non-selectively inhibited the HVA Ca²⁺ channel subtypes. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca²⁺ influx through both LVA and HVA L-type Ca²⁺ channels, in combination with the cerebral vasodilatory action, may prevent neuronal damage during ischemia.     

Postmarketing study of the use of flunarizine in vestibular vertigo and in migraine

Objective: This international postmarketing observational study of flunarizine was designed to evaluate, in routine clinical practice, the risk/benefit ratio of flunarizine in its approved indications, namely prophylaxis of migraine and treatment of vertigo. Comparator drugs were propranolol in migraine and betahistine in vertigo. The study was carried out by 498 general practitioners in Belgium, The Netherlands and Germany, whose participation had been requested by mail. In total 3186 patients were entered: 1601 in the two migraine cohorts and 1585 in the two vertigo cohorts. Results: In the migraine study, treatment results with propranolol tended to be somewhat better than those with flunarizine, but a selection bias cannot be excluded. There was no clear difference regarding efficacy between flunarizine and betahistine in the vertigo study. The safety evaluation focused on extrapyramidal symptoms (EPS) and depression. Overall, EPS were noted in only four patients, two in the vertigo-betahistine and two in the migraine-flunarizine cohort. A total of 70 patients developed depressive symptoms (34 in the flunarizine and 24 in the propranolol migraine cohorts, but only 7 in the flunarizine and 5 in the betahistine vertigo cohorts). Patients with migraine were clearly more prone to depression than patients with vertigo, regardless of their treatment. Additional risk factors for depression were a history of depression, and, in the migraine flunarizine cohort, a high number of previous migraine treatments. Received: 23 October 1995/Accepted in revised form: 20 February 1996     

葛根素治疗颈性眩晕临床观察

以葛根素加半夏白术天麻汤治疗颈性眩晕45例，为治疗组；以西北灵加半夏白术天麻汤治疗42例，为对照组。通过两组临床疗效观察：治疗组显效27例，有效16例，无效2例，有效率为96．0％；对照组显效8例，有效24例，无效10例，有效率为77．0％，对比有显著性差异（P＜0．01）。     

养血清脑颗粒联合盐酸氟桂利嗪治疗偏头痛的疗效探讨

目的：探讨养血清脑颗粒联合盐酸氟桂利嗪治疗偏头痛的临床疗效。方法将82例偏头痛患者随机分为对照组(盐酸氟桂利嗪,n=41)和观察组(盐酸氟桂利嗪+养血清脑颗粒,n=41),连续治疗1个月后,观察并对比两组的治疗效果。结果观察组的临床总有效率为92.7%,对照组的临床有效率为70.7%,对比两组有效率差异有统计学意义(字2=4.546,P<0.05)。结论养血清脑颗粒联合盐酸氟桂利嗪在临床上对偏头痛的治疗效果显著,比单独应用盐酸氟桂利嗪效果要好。     

通心络胶囊与盐酸氟桂嗪治疗偏头痛的临床对比分析

目的：研究通心络胶囊与盐酸氟桂嗪治疗偏头痛的临床治疗效果。方法整群选取2012年9月-2014年5月间在该院接受治疗的偏头痛患者288例,将其随机分为观察组和对照组,两组各有患者144例。观察组患者服用通心络胶囊进行治疗;对照组患者服用盐酸氟桂嗪胶囊。治疗结束后对比两组治疗效果。结果观察组偏头痛患者治疗前评分为(17.61±1.32),治疗后评分(6.14±2.11);对照组偏头痛患者治疗前评分为(16.94±1.59),治疗后评分为(10.51±3.12),两组偏头痛患者的数据差异有统计学意义(P<0.05)。观察组144例偏头痛患者经过治疗后,治疗后效果为控制的患者有49例(34.03%),治疗总有效率为91.67%;对照组144例偏头痛患者经过治疗后,治疗后效果为控制的患者有26例(18.06%),治疗总有效率为88.19%。两组偏头痛患者在接受治疗后治疗效果差异无统计学意义(P>0.05),但观察组控制率明显优于对照组,且差异有统计学意义(P<0.05)。结论通心络胶囊与盐酸氟桂嗪对偏头痛患者均有着较好的治疗效果,但通心络胶囊综合方面优势明显,患者控显率较高,治疗后评分优于盐酸氟桂嗪。     

110例耳鸣患者的神经内科临床治疗

目的：对该院110例耳鸣患者的神经内科临床治疗进行探究,对其治疗效果和治疗方法进行总结。方法随机选择2012年4月-2013年5月该院110例耳鸣患者作为研究对象,随机将其分成实验组和对照组,实验组50例,对照组60例。对照组患者给予常规的西比灵药物治疗,实验组患者在对照组患者治疗的基础上加用敏使朗药物,之后对两组患者的治疗效果和全血粘度性指标进行比较分析。结果实验组患者的治疗总有效率为94.00%,对照组患者的治疗总有效率是45.00%;实验组患者的血浆黏度、全血黏度低切值分别为(12.29±2.57)、(1.35±0.26);对照组患者的血浆黏度、全血黏度低切值分别为(14.93±3.54)、(1.61±0.45)。实验组患者的治疗总有效率、血浆黏度、全血黏度低切均优于对照组患者,差异有统计学意义(P<0.05)。结论西比灵联合敏使朗治疗耳鸣疾病具有积极的临床应用效果,值得实践和推广。