Feedback Stimulation of Somatodendritic Serotonin Release: A 5-HT3 Receptor-Mediated Effect in the Raphe Nuclei of the Rat

Slices from rat midbrain containing the raphe nuclei and from hippocampus were prepared, loaded with [³H]5-HT and superfused and the resting and the electrically stimulated [³H]5-HT release was measured. The 5-HT₃ receptor agonist 2-methyl-5-HT (1 to 10 μmol/l) increased the resting tritium outflow in superfused raphe nuclei slices, EC₅₀ 5.3 μmol/l. The 2-methyl-5-HT-induced increase of tritium outflow was an external Ca²⁺-independent process and was not altered by reserpine pretreatment but it was reversed by addition of the 5-HT uptake inhibitor fluoxetine (1 μmol/l). The 5-HT₃ receptor antagonists ondansetron and GYKI-46 903 (1 μmol/l) did not antagonize the stimulatory effect of 2-methyl-5-HT on resting tritium outflow. 2-Methyl-5-HT in lower concentration increased the electrically induced tritium overflow from raphe nuclei slices (EC₅₀ 0.56 μmol/l) and also from hippocampal slices preloaded with [³H]5-HT. These effects were reversed by 1 μmol/l of ondansetron and GYKI-46903. The 5-HT₃ receptor antagonists (1 μmol/l) were without effects on depolarization-evoked [³H]5-HT release at 2 Hz stimulation, when 10 Hz stimulation was used, ondansetron and GYKI-46 903 reduced the tritium overflow from raphe nuclei slices. These data indicate that 5-HT₃ receptors positively alter depolarization-induced somatodendritic 5-HT release in the raphe nuclei. They also show that 2-methyl-5-HT is able to evoke 5-HT release not only from vesicles but also from cytoplasmic stores via a transporter-dependent exchange process.     

Randomised controlled trial of ondansetron in smoking cessation

A double-blind, placebo controlled trial was undertaken to examine the effect of the 5-HT₃ antagonist, ondansetron .25 mg bd on cigarette withdrawal symptoms and on proportion of individuals maintaining continuous abstinence for 4 weeks in a smoking treatment programme. A total of 111 smokers were allocated to active or placebo conditions and began taking their study medication 2 weeks before the quit date. They attended the smokers clinic for weekly group treatment sessions. The results showed no evidence for less severe withdrawal symptoms or improved abstinence rates in the active medication group. They suggest that inhibiting 5-HT₃ activity is not an effective method of controlling nicotine withdrawal or helping smokers to stop.     

盐酸恩丹西酮缓释片的研制及体外释药特性

制备盐酸恩丹西酮缓释片并对影响释药的因素进行考察。以羟丙甲纤维素（HPMC）为骨架材料制备了盐酸恩丹西酮缓释片，通过正交设计试验优选最佳处方和工艺。对影响释药的因素，如HPMC的黏度和用量、填充剂的种类、制片工艺、润湿剂及释放介质pH等进行了考察。盐酸恩丹西酮缓释片体外释药符合Higuchi方程，HPMC的黏度、填充剂的种类及测定释放度的转速对该缓释片的释药几乎无影响，而制片工艺、润湿剂及释放介质pH值对缓释片释药影响较大。盐酸恩丹西酮缓释片在体外12h缓释效果较好。     

三种药物防治胃肠肿瘤化疗所致呕吐的临床研究

目的：评价三种药物防治胃肠肿瘤化疗所致呕吐的价值。方法：９０名患者随机分成三组,灭吐灵组（Ａ组）,吗丁啉组（Ｂ组）,枢丹组（Ｃ组）。应用５－Ｆｕ＋ＬＶ方案化疗５天,观察５天内三种药物的止吐效果。结果：Ａ和Ｂ、Ｃ组比较有显著性差异（Ｐ〈０．０５）,Ｂ和Ｃ比较无显著性差异（Ｐ〉０．０５）。结论：Ｂ组副作用少,疗效高,建议临床推广使用吗丁啉。     

国产四类新药盐酸格拉司琼注射液与恩丹西酮预防化疗引起的恶心和呕吐的疗效比较

目的 验证国产盐酸格拉司琼注射预防恶性肿瘤患者化疗所致恶心与呕吐的有效性和安全性。方法 对６９例接受以顺铂为主化疗和４０例接受以蒽环类抗肿瘤药为主化疗的恶性肿瘤患者,采用前瞻性多中心随机对照试验,比较国产格拉司琼和国产上市恩丹西酮预防化疗所致恶心与呕吐的疗效和不良反应。结果 格拉司琼和恩丹西酮对预防强致吐和中度致叶化疗药物所致的急性和迟发性恶心与呕吐的疗效基本相同;不良反应变基本相似,以便秘、疲倦     

恩丹西酮（齐鲁）预防非顺铂化疗所致呕吐的Ⅲ期临床研究

目的改进用药方法,进一步确定恩丹西酮的临床应用价值。方法首次用非顺铂药出现呕吐者为入组对象。再次化疗时,给予恩丹西酮（齐鲁）８ｍｇ静脉注射,每日１次。化疗结束后口服８ｍｇ,每日２次,用１天的简化方法。结果经多中心１９３例患者应用,第１天止吐有效率达９３．３％,对迟发性呕吐也有很好疗效。第１～５天平均呕吐次数为０．４～０．０１。结论本法疗效高,副作用小,且经济方便,更适于临床推广应用。     

Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer

Purpose: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy. Methods: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted. Results: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml · min) were lower than those of the control patients (88.3 mg/ml · min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only. Conclusion: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed. Received: 28 October 1997 / Accepted: 9 March 1998     

盐酸恩丹西酮包芯缓释片的研制

目的　研制盐酸恩丹西酮包芯缓释片。方法　采用HPMC为骨质材料,通过正交设计试验优选最佳处方和工艺,考察释放介质pH值对缓释片释药特性的影响。结果及结论　释放介质pH值对盐酸恩丹西酮包芯缓释片释药影响较大,在酸性介质及中性蒸馏水中 2 4h释药完全(≥ 95 %),在 pH6 8磷酸盐缓冲液中释药不完全( <4 5 % ),0～ 14h体外释放符合零级动力学过程。     

帕洛诺司琼联合地塞米松预防中度致吐化疗引起恶心呕吐的临床研究

目的 观察和评价帕洛诺司琼联合地塞米松预防中度致吐化疗方案所致恶心、呕吐(CINV)的临床疗效和不良反应.方法 60例患者采用中度致吐方案化疗,按随机抽样法随机分为帕洛诺司琼组和昂丹司琼组,各30例.帕洛诺司琼组给予盐酸帕洛诺司琼0.25 mg,第1天化疗前30 min静脉注射.昂丹司琼组给予盐酸昂丹司琼8 mg,化疗前30 min缓慢静脉滴注,连用3d.2组均联合地塞米松5 mg静脉注射.观察5d内恶心、呕吐等不良反应发生情况并作比较.结果 帕洛诺司琼组与昂丹司琼组急性CINV完全缓解率分别为80.0％ (24/30)和76.7％(23/30),有效控制率分别为93.3％(28/30)和86.7％(26/30),差异无统计学意义(P＞0.05);延迟性CINV完全缓解率分别为76.7％ (23/30)和63.3％(19/30),差异无统计学意义(P＞0.05),有效控制率分别为93.4％(28/30)和73.3％(22/30),差异有统计学意义(P＜0.05).2组不良反应发生率均较低,组间差异无统计学意义(P＞0.05).结论 帕洛诺司琼预防中度致吐化疗方案所致急性CINV 疗效与昂丹司琼相当,对延迟性CINV 的疗效优于昂丹司琼,不良反应程度较轻、安全性好.     

莫沙必利与昂丹司琼联合治疗2型糖尿病胃轻瘫的临床观察

目的：观察莫沙必利与昂丹司琼联合治疗糖尿病胃轻瘫的疗效。方法：将60例2型糖尿病胃轻瘫患者,依照入院的先后顺序随机分为2组。观察组（30例）患者给予莫沙必利与昂丹司琼联合治疗,对照组（30例）患者给予莫沙必利治疗,疗程2周,对患者治疗前后的临床症状进行评分。结果：治疗后,观察组患者临床症状评分显著低于对照组[（0．70±0．57）分相比（1．14±0．73）分,P＜0．05],总有效率明显高于对照组[80．00％（24／30）相比50．00％（15／30）,P＜0．05]。结论：莫沙必利与昂丹司琼联合治疗糖尿病胃轻瘫的疗效较莫沙必利单药治疗更好。