Effect of peripheral administration of cinnarizine and verapamil on the abstinence syndrome in diazepam-dependent rats

The effects of two calcium channel blockers (verapamil and cinnarizine) were evaluated on diazepam withdrawal symptoms. Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg IP for 3 weeks. On abrupt termination of the drug, animals showed withdrawal hyperactivity that was assessed by autonomic, behavioural and motor signs. The peak effect was seen 3 days after the withdrawal of diazepam. On IP administration, verapamil and cinnarizine (10, 20 and 40 mg/kg) given on eight occasions at an interval of 12 h reversed the withdrawal-induced increase in spontaneous motor activity. Cinnarizine in higher doses (20 and 40 mg/kg) was found to be effective in suppressing the behavioural signs but verapamil did not show any protective effect against startle response and irritability. These results suggest that modulation of the calcium influx in the CNS might influence withdrawal.This study was presented in XIth International Congress of Pharmacology (IUPHAR) at Amsterdam (July 1–6, 1990)     

脑益嗪对实验性血栓形成的影响

脑益嗪是—钙拮抗剂。本实验用颈动—静脉血流旁路术和改良的chandler氏体外血栓法研宄了脑益嗪的抗血栓作用。结果表明:脑益嗪对两种方法形成的血栓均有明显的抑制作用,二种方法的结果基本一致。因此,本文提示脑益嗪除直接扩张血管外,尚有很强的抗血栓作用,其效价强度优于阿斯匹林。     

几种中西药抗人实验模拟运动病效果观察

目的 :选用中药“治晕灵”的主要成分生姜、明天麻等六味草药煎成汤剂、或半量汤剂配西药脑益嗪、山莨菪碱各1 4临床常用量配成复方中西药制剂 ,与目前常用抗晕药晕海宁等中、西药的药效进行比较 ,看中药制剂或中西药复方制剂是否具有较好的抗运动病效果。方法 :选 7名敏感被试者 (女性 ,19～ 2 1岁 ) ,用旋转刺激诱发运动病至出现恶心。按拉丁方设计 ,与安慰剂 (淀粉 10 0mg)及晕海宁 (5 0mg)进行对比 ,分别观察了生姜合剂 (30ml)、晕可平 (30ml)、山莨菪碱 (10mg)、脑益嗪 (2 5mg)及上述复方中西药制剂口服后的运动病耐力。结果 :与安慰剂比较 ,晕海宁、山莨菪碱、脑益嗪、晕可平、生姜合剂、复方中西药制剂分别使运动病耐力提高 5 .4%、7.5 %、5 .9%、7.4%、32 .3 %、2 0 .4% ;生姜合剂效果较优 ,除口服时有辛辣味外 ,无明显的副作用。复方中西药制剂各成分未显示协同作用 ,而只是简单的作用相加。结论 :生姜合剂具有较好的抗运动病作用     

Exploring the feasibility of the use of biopolymers as a carrier in the formulation of amorphous solid dispersions – Part I: Gelatin

Biopolymers have rarely been used so far as carriers in the formulation of amorphous solid dispersions (ASD) to overcome poor solubility of active pharmaceutical ingredients (APIs). In an attempt to enlarge our knowledge on this topic, gelatin, type 50PS was selected. A screening study was initiated in which twelve structurally different poorly soluble biopharmaceutical classification system (BCS) Class II drugs (carbamazepine, cinnarizine, diazepam, itraconazole, nifedipine, indomethacin, darunavir (ethanolate), ritonavir, fenofibrate, griseofulvin, ketoconazole and naproxen) were selected for evaluation. Solid dispersions of five different drug loadings of these twelve compounds were prepared by lyophilization and evaluated for their solid state properties by mDSC and XR(P)D, and in vitro dissolution performance. Even without any process optimization it was possible to form either fully amorphous or partially amorphous systems, depending on the API and API to carrier ratio. Hence in this respect, gelatin 50PS behaves as any other carrier. Dissolution of the API from the solid dispersions significantly exceeded that of their crystalline counterparts. This study shows the potential of gelatin as a carrier to formulate amorphous solid dispersions.     

Determination of certain drugs in binary mixtures formulations by second derivative ratio spectrophotometry and LC

Spectrophotometric and high-performance liquid chromatographic (HPLC) methods are developed for simultaneous determination of three binary mixtures with overlapping spectra. The spectrophotometric method is based on the use of second derivative of the ratio spectra (2DD) for resolution of three binary mixtures of indapamide with captopril (mixture 1), cinnarizine with heptaminol acefylline (mixture 2) and amoxycillin trihydrate with flucloxacillin sodium (mixture 3). The HPLC method depends on the separation of components of binary mixtures using ODS column with mobile phase consisting of acetonitrile and 5 mM aqueous heptane sulphonic acid sodium salt in ratios of (60:40, v/v, pH 5.5) for mixture 1, (50:50, v/v, pH 3.0) for mixture 2 and (35:65, v/v, pH 4.2) for mixture 3. The proposed methods are accurate, non-destructive and successfully applied for the determination of the three binary combinations in synthetic mixtures and commercial pharmaceutical products.     

Spectrophotometric and LC determination of two binary mixtures containing antihistamins

Several methods are developed for the determination of two binary mixtures containing cyclizine hydrochloride with pyridoxine HCl (mixture (mix.) 1); and cinnarizine with piracetam (mix. 2). The resolution of the two binary mixtures has been accomplished by using numerical spectrophotometric methods as partial least squares (PLS-1) and principal component regression applied to UV spectra of the mixture and graphical spectrophotometric method as second derivative of the ratio spectra (2DD). In addition, HPLC methods were developed depending on using RP18 column with mobile phase consisting of acetonitrile/0.05 M KH2PO4 (50:50, v/v, pH 4.0) with UV detection at 239 nm for mix. 1, and mobile phase consisting of acetonitrile/0.05 M KH2PO4/triethylamine (50:50:0.2, v/v/v, pH 3.0) with UV detection at 227 nm for mix. 2. The proposed methods were successfully applied for the determination of the two binary combinations in synthetic mixtures and commercial tablets.     

Selective effect of cinnarizine on the vestibular nucleus neurons

Summary Effects of cinnarizine were studied on the lateral vestibular nucleus (LVN) and spinal trigeminal nucleus (STN) of cats anesthetized with -chloralose. Cinnarizine did not produce any obvious alterations of the field potential and spike generation of type B interneurons in STN elicited by trigeminal nerve stimulation as well as the field potential in LVN by vestibular nerve stimulation. Spike generation of monosynaptic LVN neurons elicited by the suprathreshold stimulus to the vestibular nerve was unaffected by cinnarizine up to 4 mg/kg. When the subthreshold stimulus was applied to the vestibular nerve, however, the spike number of LVN monosynaptic neurons was significantly increased after cinnarizine treatment. The enhancement of spike firing by cinnarizine upon both supra- and subthreshold stimuli to the vestibular nerve was found to be more pronounced in LVN polysynaptic neurons than monosynaptic ones. Since the effect of cinnarizine on LVN neurons was not dose-dependent, it is suggested that the enhanced responsiveness of the neurons by the drug might be due to an increase of blood flow, but not to a direct excitation of the neurons themselves.     

黛力新联合西比灵治疗偏头痛疗效观察

目的:评价黛力新联合西比灵治疗偏头痛的临床效果。方法:将100例偏头痛患者随机分成两组,治疗组服黛力新每日2片,早晨、中午各1次;服西比灵5mg,每晚1次。对照组只服西比灵5mg,每晚1次。结果:治疗组能显著减少头痛发作次数(P<0.05),显著减轻头痛程度(P<0.05),缩短头痛发作持续时间(P<0.05)。结论:黛力新联合西比灵治疗偏头痛疗效优于单独应用西比灵,且无严重副反应。     

流式细胞术分析脑益嗪对成纤维细胞的调控作用

用流式细胞术测定不同剂量的脑益嗪（ＣＩＮ）对培养中３Ｔ６成纤维细胞的影响，包括检测细胞生长周期、ＤＮＡ含量、分裂增值指数及Ｇ１期和Ｇ２期蛋白质含量的变化。发现用脑益嗪后Ｇ１期细胞数增加，而Ｓ期细胞数减少，但无明显的量效关系；ＤＮＡ含量及分裂增殖指数下降；Ｇ１期及Ｇ２期蛋白质含量明显高于对照组。结果表明，脑益嗪可阻滞Ｇ１→Ｓ进程，使细胞堆积于Ｇ１期，减少ＤＮＡ含量及细胞分裂，增加蛋白质含量，使３Ｔ６细胞呈现不平衡生长状态。     

黛立新与西比灵预防性治疗偏头痛疗效比较

目的比较黛立新与西比灵预防性治疗偏头痛的疗效。方法选择头痛影响测定-6评分大于60分的偏头痛患者92例,随机分为黛立新组和西比灵组。黛立新组予以黛立新早餐后服用,每天1片;西比灵组予西比灵每晚9时服用,每天10mg。治疗5周,以问卷“头痛影响测定-6（HIT-6）”于治疗后再次对患者进行评分。结果两组治疗后的HIT-6评分差异有高度统计学意义（P〈0．01）,黛力新组HIT-6评分减少更明显。结论对头痛影响测定-6评分大于60分的患者,黛立新预防性治疗偏头痛的疗效优予两比灵。