A fully automated light/dark apparatus useful for comparing anxiolytic agents

The effects of known anxiolytic agents and putative anxiolytic agents were assessed in mice in a fully automated 2-compartment light/dark test. Significant increases in lit area activities (e.g., time spent in the lit area, locomotor activity, rearing behavior) were used as possible indicators of anxiolytic-like action. The measurement found most consistent and useful for assessing antianxiety-like activity was the time mice spent in the lit area. The benzodiazepine, diazepam; the 5-HT1A agent, ipsapirone; and the 5-HT3 receptor antagonist, ondansetron, produced significant anxiolytic-like activity between doses of 1.0 to 10.0 mg/kg, 17.8 to 31.6 mg/kg, and 0.0001 to 1.0 mg/kg respectively. The 5-HT1A receptor agonist, 8-OH DPAT, also exhibited anxiolytic-like action between doses of 0.0005 to 3.16 mg/kg. In contrast, the peripheral 5-HT3 receptor agonist, N-phenylbiguanide; the antidepressant, imiprame; the neuroleptic, chlorpromazine; and the CNS stimulat, S(+)-amphetamine, did not display antianxiety-like activity. The positive results obtained for the three types of compounds (benzodiazepine, 5-HT1A, and 5-HT3) indicate that this fully automated light/dark apparatus may be useful for identifying known and putative anxiolytic agents.     

枢丹预防大剂量顺铂化疗所致呕吐的临床效果

目的观察枢丹的止吐疗效和毒性。方法对３０例接受大剂量顺铂化疗的患者,采用随机自身对照的方法,比较枢丹和枢复宁在相等剂量下的疗效和毒性。结果枢丹能有效预防顺铂所致的恶心、呕吐,其止吐效果与枢复宁相似。两药的止吐有效率分别为７０．０％和６３．３％,完全缓解率分别为５６．７％和５３．３％。两药的疗效无统计学差异,且毒副反应小。结论枢丹为肿瘤化疗安全、有效的止吐药,值得临床推广应用     

Gastroprokinetic properties of the benzimidazolone derivative BIMU 1, an agonist at 5-hydroxytryptamine4 and antagonist at 5-hydroxytryptamine3 receptors

We have investigated the in vivo motor stimulating and gastroprokinetic properties of the azabicycloalkyl benzimidazolone derivative BIMU 1 (3-ethyl-2,3dihydro-N-(8-methyl-8-azabicyclo [3.2.1] oct-3-yl)-2-oxo 1H-benzimidazole-1-carboxamide hydrochloride) and its binding profile at 5-hydroxytryptamine₃ and 5-hydroxytryptamine₄ receptors, in an attempt to assess the serotonergic mechanism underlying its prokinetic action.BIMU 1 dose-dependently (0.01–0.3 mg/kg iv.) increased the motility of a denervated pouch of canine stomach. This excitatory action was sensitive to muscarinic blockade. A similar stimulatory effect was exerted by the benzamidic prokinetic agent cisapride (0.03–0.3 mg/kg i.v.) but not by the 5-HT₃ receptor antagonist ondansetron (up to 1 mg/kg i.v ). The significance for propulsive efficacy of the motor stimulating activity of BIMU 1 was evaluated in a model of gastric emptying of liquids in the conscious dog. The emptying rate of a non-caloric liquid meal instilled through a gastric fistula was accelerated by both BIMU 1 (0.01–1 mg/kg i.v. and 0.1–3 mg/kg p.o.) and cisapride (0.03–1 mg/kgiv.and0.3–10 mg/kgp.o.).Ondansetron (1 mg/kg i.v.) did not show any effect. The activity of the 5-HT₄ receptor antagonist DAU 6285 was evaluated in the gastric emptying model per se and in interaction experiments on the accelerating action of BIMU 1 (0.3 mg/kg L v.). At 1 mg/kg iv., DAU 6285 was ineffective on its own and failed to antagonize BIMU 1-induced prokinetic action;at the dose of 3 mg/kg i.v., it depressed the gastric emptying rate per se by 15% and totally abolished the accelerating effect of BIMU 1.In the binding assay, BIMU 1 exhibited an appreciable affinity for 5-HT3 receptors in NG 108-15 cells (K_D: 0.8 nmol/l) and for 5-HT₄ receptors in pig striatum (K_D: 26.5 nmol/l). Compared to BIMU 1, cisapride bound with a similar affinity to 5-HT₄ (K_D: 35.2 mnol/l) and a much lower affinity to 5-HT₃ receptors (K_D: 155 nmol/l). By contrast, ondansetron was highly selective for 5-HT₃ sites (K_D: 4.7 nmol/l), being ineffective in the assay for 5-HT₄ receptors (K_D > 10000).Our results show that BIMU 1, like cisapride and unlike ondansetron, is an effective stimulant of gastric motility and propulsion. The action of BIMU 1 appears to depend on 5-HT₄ receptor stimulation and to involve the activation of cholinergic nerve pathways. Correspondence to: C. A. Rizzi at the above address     

国产甲孕酮加强预防化疗消化道反应的效果比较

目的 :比较恩丹西酮、恩丹西酮 地塞米松、恩丹西酮 地塞米松 国产甲孕酮 (倍恩胶囊 )三种止吐方案预防化疗消化道反应的疗效。方法 :以中等剂量顺铂或阿霉素为主化疗的患者 90例 ,随机分成三组 ,每组 30例 ,分别使用上述止吐方案 ,观察其预防化疗消化道反应的效果。结果 :对于呕吐 ,单用恩丹西酮、恩丹西酮 地塞米松、恩丹西酮 地塞米松 倍恩胶囊三个方案的有效率相近 ,分别为 80 %、87%、90 % ;对于恶心 ,三个方案的有效率分别为 6 3%、80 %、90 % ,差别具有显著性 (χ2 =6 .3,P <0 0 5 ) ;对于食欲不振 ,三个方案的有效率分别为 17%、5 3%、80 % ,有极显著差异 (χ2 =2 4 .2 7,P <0 0 0 5 )。结论 :单独使用恩丹西酮不足以完全预防化疗消化道反应 ,加用地塞米松后效果有所提高 ,但以恩丹西酮 地塞米松 倍恩胶囊最好 ,特别是预防化疗恶心和食欲不振明显优于单用恩丹西酮或恩丹西酮 地塞米松     

Ondansetron,an antagonist of 5-HT3 receptors,antagonizes the anti-exploratory effect of caerulein,an agonist of CCK receptors,in the elevated plus-maze

Systemic treatment with caerulein (0.25–5 µg/kg SC), non-selective agonist of cholecystokinin (CCK) receptors, dose-dependently suppressed the exploratory behaviour of rats in an elevated plus-maze without producing remarkable changes in the locomotor activity of animals in an open field test. Ondansetron, a selective antagonist of 5-HT₃ receptors, increased the number of open arm entries in the plus-maze test only at a dose 10 µg/kg. The other doses of ondansetron (0.1, 1 and 100 µg/kg IP) did not significantly change either the locomotor activity or the exploratory behaviour of rats. Pretreatment of rats with ondansetron (at 10 µg/kg, but not at 0.1, 1 or 100 µg/kg) completely reversed the anti-exploratory effect of caerulein (5 µg/kg). The concomitant treatment with caerulein and ondansetron did not cause any major change in the locomotor activity of animals in open field. Consequently, we propose that 5-HT-ergic mechanisms are involved not only in the regulation of CCK release in the cerebral cortex and nucleus accumbens, but also in the modulation of the anti-exploratory effect of caerulein, a CCK agonist, in the elevated plus-maze.     

帕洛诺司琼在鼻咽癌同步放化疗中防治恶心呕吐的疗效观察

目的：对接受同步放化疗的鼻咽癌患者采用帕洛诺司琼预防恶心呕吐,观察其治疗效果。方法将行同步放化疗的鼻咽癌患者80例随机分为2组,分别采用帕洛诺司琼和昂丹司琼止吐治疗,观察并比较2组患者发生急性、延迟性恶心呕吐及其他不良反应的情况。结果帕洛诺司琼组急性恶心发生率为57．5％、急性呕吐32．5％,昂丹司琼组急性恶心、呕吐的发生率为62．5％、35．0％,2组比较差异无统计学意义（P＞0．05）;帕洛诺司琼组延迟性恶心、延迟性呕吐发生率分别为80．0％、62．5％,昂丹司琼组延迟性恶心、呕吐的发生率为87．5％、80．0％,帕洛诺司琼组明显降低,差异有统计学意义（P＜0．05）。除恶心、呕吐的消化道反应外,2组患者均出现头晕、口干、头痛、乏力、低热、便秘、焦虑、腹泻等放化疗相关不良反应,2组的不良反应发生率无明显差异（P＞0．05）。结论对接受同步放化疗的鼻咽癌患者采用帕洛诺司琼,能够预防放化疗引起的急性及延迟性恶心呕吐,尤其是能够有效控制延迟性恶心呕吐的发生,且不良反应轻微,值得在临床上推广使用。     

盐酸恩丹西酮鼻用凝胶剂的制备与质量控制

目的设计盐酸恩丹西酮鼻用凝胶剂处方,并建立其质量控制方法.方法以卡波姆-940和甘油作为凝胶基质和主要辅料,用三乙醇胺调节pH值,制备盐酸恩丹西酮鼻用凝胶剂,采用紫外分光光度法对凝胶剂中盐酸恩丹西酮的含量进行测定.结果所得凝胶剂质量稳定,含量准确,盐酸恩丹西酮平均回收率为100.15%.结论该制剂制备工艺简便、稳定性好,质量控制方法简便、快速、准确.     

恩丹西酮（Ondanstron）预防顺铂呕吐Ⅱ期临床研究

采用自身随机交替对照方法，观察了恩丹西酮的止吐作用。４４例患者入组，顺铂剂量为５０ｍｇ／次，连用３天，患者在第一周期随机接受恩丹西酮或胃复安止吐方案，在第二周期时交替止吐方案。结果显示，恩丹西酮控制急性恶心呕吐优于胃复安方案，９５％的患者有效，而对照组仅５０％有效。恩丹西酮组没有观察到锥体外系症状，而对照组中有３例出现锥体外系症状。     

Serotonergic modulation of anticholinergic effects on cognition and behavior in elderly humans

Cholinergic neurotransmission is thought to be modulated by serotonin as documented in animal and human studies. We examined the effects of the muscarinic antagonist scopolamine (0.4 mg IV) given alone or together with the serotonin mixed agonist/antagonistm-chlorophenylpiperazine (m-CPP, 0.08 mg/kg IV), and the selective 5-HT₃ receptor antagonist ondansetron (0.15 mg/kg IV). Ten normal elderly volunteers each received five separate pharmacologic challenges (placebo, ondansetron, scopolamine, scopolamine + ondansetron, and scopolamine + m-CPP). Cognitive, behavioral, and physiologic variables were analyzed using repeated measures analysis of variance. The acute effects of scopolamine in certain cognitive, behavioral, and physiological measures were significantly exaggerated by the addition of m-CPP. Scopolamine's cognitive effects were unaffected by ondansetron at the dose tested, nor did ondansetron given alone affect basal cognitive performance. This pilot study suggests that the serotonin mixed agonist/antagonist m-CPP may influence cholinergic neurotransmission. The changes associated with the combination of scopolamine and m-CPP do not appear to be secondary to simple pharmacokinetic alterations and suggest a complex interaction between the cholinergic and serotonergic systems centrally.     

雷莫司琼预防肺癌顺铂化疗所致恶心呕吐效果的随机对照临床研究

背景与目的顺铂对各种恶性肿瘤都有明显疗效,是肺癌联合化疗的常用药物。但它所引起的严重的恶心、呕吐成为临床应用顺铂的一个剂量限制因素。新一代止吐药物5-HT3受体拮抗剂雷莫司琼可以减轻顺铂化疗引起的恶心呕吐。为了观察雷莫司琼注射剂预防顺铂化疗所致恶心呕吐的临床疗效,我们进行了临床观察,并与恩丹西酮进行对照。方法采用随机平行对照方法,100例患者随机分为雷莫司琼组50例和恩丹西酮组50例。雷莫司琼0.3mg化疗前30min静脉冲入,恩丹西酮8mg化疗前15min和化疗结束时静脉冲入。结果雷莫司琼对顺铂所致恶心的控制率在第1~3天分别为82%、72%、84%,恩丹西酮分别为84%、70%、76%,两药疗效相似。雷莫司琼对呕吐控制的有效率在第1~3天分别为88%、86%、90%,恩丹西酮分别为80%、76%、86%,雷莫司琼对呕吐的有效率高于恩丹西酮,但无统计学上差异。两药不良反应的发生率相似。结论雷莫司琼能有效预防顺铂化疗引起的恶心呕吐,其疗效略优于恩丹西酮。