中国林蛙卵油抗士的宁惊厥的机制

目的揭示CO2超临界萃取的中国林蛙卵油(Rana temporaria chensinensis Davidegg oil,EORTCD)抗士的宁惊厥作用的机制。方法以士的宁为致惊剂,评价中国林蛙卵油抗惊厥活性的时效和量效关系。通过利血平耗竭单胺神经递质和奥单西隆阻断5-HT3受体,在士的宁致惊厥的小鼠模型中探讨中国林蛙卵油抗惊厥作用机制。结果中国林蛙卵油给予动物30 min,其抗惊厥作用效果最好。中国林蛙卵油抗惊厥作用呈现良好的剂量-效应关系;利血平耗竭单胺递质后,EORTCD对抗士的宁惊厥的效应消失;奥丹西隆阻断5-HT3受体后,再给EORTCD 1.4 g.kg-1,EOTCD的抗士的宁惊厥作用也被阻断。而高剂量组EORTCD未受奥丹西隆阻断。结论高、低剂量EORTCD抗惊厥作用可能启动不同的通路。低剂量EORTCD抗士的宁惊厥可能与5-HT3受体有关。     

中国林蛙卵油的抗焦虑作用

目的研究中国林蛙卵油 (eggoilofRanatemporariachensinensisDavid ,EORTCD)的抗焦虑作用。方法应用高架十字迷路和小鼠爬梯实验评价中国林蛙卵油的抗焦虑活性及其量效、时效关系。结果与对照组比较 ,EORTCD 2 0、4 0 g·kg-1能显著延长大鼠在十字迷路开放通路连续停留时间 ,增加大鼠进入开放通路次数 ,而对封闭通路连续停留时间和进入封闭通路次数无明显影响 ;小鼠爬梯实验中 ,EORTCD 1 4～5 6g·kg-1组小鼠站立数明显减少而爬梯数无显著差异 ;EORTCD抗焦虑时效实验表明在给药后 3 0、60min抗焦虑活性较强 ;γ 氨基丁酸 (γ aminobutyricacid ,GABA) 5 0、1 0 0mg·kg-1分别与EORTCD 1 2 g·kg-1联合给药组的小鼠站立数显著降低而爬梯数无显著减少 ,且比单独给予EORTCD组小鼠站立数少。结论中国林蛙卵油有明显抗焦虑作用。     

实验研究天南星抗惊厥作用

目的：研究天南星在不同温度下的抗惊厥作用。方法：以对抗士的宁引起小鼠强直性惊厥及死亡的指标。比较研究了天南星不同温度提取的水溶液的抗惊厥作用。结果：发现天南星冷水浸出物对士的宁引起小鼠惊厥有明显抑制作用,且可明显降低惊厥的死亡率。     

石菖蒲醇提取物的抗惊厥作用

目的：研究石菖蒲醇提取物的抗惊厥作用。方法：采用最大电休克发作（ＭＥＳ）法,士的宁惊厥法和戊四氮最小阈发作（ＭＥＴ）法,观察石菖蒲醇提取物对动物惊厥的影响。结果;石菖蒲醇提取物能明显对抗大鼠,小鼠的最大电休克发作和小鼠的戊四氮最小阈发作及士的宁的惊厥的反应。结论;石菖蒲醇提取物具有明显的抗惊厥作用。     

东亚钳蝎毒及其成分抗癫痫肽的抗惊厥作用

本文报道了河北产东亚钳蝎毒及从粗毒中纯化的抗癫痫肽的抗惊厥作用,本实验用咖啡因、美解眠、士的宁引起惊厥,用生理盐水作空白对照,安定做阳性对照。生理盐水对照组,惊厥发生率均达100%;严重惊厥发作率分别为50%、70%、50%;死亡率分别为40%、30%、50%,各组惊厥平均总持续时间为115min、59.5min、72min。安定对抗咖啡因惊厥的作用较小(P>O.05);但使美解眠和士的宁惊厥各项指标显著下降(P<0.05)。抗癫痫肽对抗咖啡因惊厥的作用较强,四项指标均显著下降(P<0.01),使美解眠惊厥各项指标亦明显下降(P<0.01),但稍弱;对抗士的宁惊厥的作用强度与安定相似(P<0.05)。蝎毒的抗惊厥作用较抗癫痫肽弱,与空白对照组比较差异不显著。     

木防己碱对中枢神经系统影响的实验观察

本文观察到Tr具有抑制小鼠的自主活动,加强戊巴比妥钠及水合氯醛对中枢的抑制作用,拮抗咖啡因与苯丙胺的兴奋作用,推迟出现戊四氮和士的宁惊厥的潜伏期,延长士的宁致小鼠惊厥后死亡的时间,本品尚有镇痛和降温作用,表明Tr具有镇静、镇痛、降温等中枢抑制作用。     

羚羊清热液镇静和抗惊厥作用实验研究

目的:研究羚羊清热液的镇静和抗惊厥作用.方法:对正常小鼠或苯丙胺兴奋小鼠通过测定给药后的自主活动观察羚羊清热液的镇静作用;采用回苏灵、苯甲酸钠咖啡因等小鼠惊厥模型,观察羚羊清热液的抗惊厥作用.结果:羚羊清热液26,52 g/kg(折算成生药,下同)能明显减少正常小鼠以及苯丙胺兴奋小鼠的自主活动,与戊巴比妥钠合用有一定的协同睡眠作用,并明显延长回苏灵和苯甲酸钠咖啡因所致小鼠惊厥的潜伏期和死亡时间.结论:羚羊清热液具有一定镇静和抗惊厥作用.     

滋肾宁神丸抗小鼠和大鼠惊厥的作用

中成药滋肾宁神丸4g/(kg·d)灌胃能显著降低最大电休克致小鼠惊厥率和筒箭毒碱侧脑室注射致大鼠惊厥率;2g/(kg·d)和4g/(kg·d)灌胃能明显减少ip 士的宁致小鼠惊厥率,4g/(kg·d)和8g/(kg·d)灌胃能明显延长ip 戊四唑至小鼠惊厥的诱导期,但对电刺激小鼠足部引起的小鼠激怒行为无影响。表明滋肾宁神丸具有明显的安神、抗惊厥作用。     

镇痫灵片抗癫痫作用的实验研究

目的 :探讨镇痫灵片抗癫痫作用。方法 :采用小鼠自发活动法 ;戊巴比妥钠阈下催眠法、致惊剂 (士的宁、戊四氮 )诱发惊厥法、最小休克发作法和最大电休克发作法。结果 :镇痫灵片能明显抑制小鼠自发活动 ;增加阈下剂量戊巴比妥钠的睡眠鼠数 ;并能降低阈剂量士的宁的致惊率和小鼠戊四氮 CD50 ,提高小鼠最小休克阈值。结论 :本品具有镇静、抗惊厥作用     

加巴喷丁片剂的主要药效学研究

目的　研究国产新药加巴喷丁 (GBP)的主要药效学。方法　抗惊厥试验采用最大电休克发作法 (MES)、士的宁惊厥法及戊四唑最小发作法 (MET)。结果　GBP片剂 (30～ 96 0mg·kg-1,ig)呈剂量依赖性对抗小鼠的MES及MET ;GBP片剂 (6 0～ 480mg·kg-1,ig)也能对抗士的宁引起的小鼠惊厥。结论　GBP片剂有明显的抗惊厥作用。     

Anticonvulsant profile of drugs which facilitate GABAergic transmission on convulsions mediated by a GABAergic mechanism

The effects of selected modulators of GABAergic transmission, either alone or in combination, were tested for their potency on the seizure pattern and mortality induced by convulsant drugs in rat. Pentobarbital and diazepam were effective against both tonic and clonic seizure components induced by bicuculline and picrotoxin. The anticonvulsant profile of ethanol closely resembled that of pentobarbital. Pentobarbital, diazepam and ethanol did not modify seizures induced by strychnine. In contrast, progabide, a central gamma-aminobutyric acid (GABA) receptor agonist, caused significant protection only against convulsions induced by strychnine and its lethality, but did not protect against seizures induced by bicuculline or picrotoxin. Data on interaction of drugs with subprotective doses of these agents clearly demonstrated potentiation of the anticonvulsant actions of these modulators. Thus, seizures induced by bicuculline were more sensitive to the inhibition by pentobarbital in combination with diazepam or ethanol, while pentobarbital with progabide was equally effective against convulsions induced by GABA antagonists. Diazepam, in combination with progabide, blocked only convulsions induced by picrotoxin. Ethanol, in combination with either pentobarbital or with diazepam, was effective against all the three convulsant drugs. These results are consistent with the concept that drugs which facilitate GABAergic transmission are effective against seizures related to an impairment of GABA transmission. Further, the present data indicate that tonic seizures are more susceptible to the actions of drugs than the clonic component. Smaller doses of these drugs, alone or in combination, modified the seizure patterns and mortality, whereas at larger doses, the possible involvement of a nonspecific depressant action cannot be ruled out.     

The effects of convulsant and anticonvulsant treatments on the behavioural effects of ultrasound presentation in Lister hooded rats

Lister hooded rats exhibit bursts of locomotion when exposed to a 20 kHz acoustic stimulus; this ultrasound-induced locomotion has been suggested as a potential model for panic attacks. The present studies determined the effects of treatment with the convulsant agents strychnine and pentylenetetrazole and the anticonvulsant agents pentobarbital and ethosuximide on locomotor behaviour elicited by experimenter-presented ultrasounds in Lister hooded rats. Behaviour in a circular arena was viewed live and tracked electronically. In Experiment 1, brief exposure to an ultrasound stimulus typically resulted in short intensity-related bursts of locomotion in control rats. Pentobarbital or ethosuximide treatment reduced this short-term ultrasound-induced locomotion in a dose-related manner, whereas pentylenetetrazole or strychnine treatment increased these locomotor bursts. In Experiment 2, exposure to the ultrasound stimulus for a longer period resulted in irregular cycles of bursts of locomotion followed by periods of relative inactivity in control rats. In addition, approximately 10% of control rats exhibited convulsions associated with this long-duration ultrasound exposure at 98 dB sound pressure level. Sub-convulsant doses of the convulsant treatments increased the frequency of occurrence of convulsions associated with the ultrasound stimulus; pentobarbital or ethosuximide pretreatment significantly reduced this effect. The present findings suggest that a relationship exists between ultrasound-induced locomotor bursts and convulsant activity.     

灵芝颗粒剂对小鼠镇静催眠和免疫功能的影响

目的：观察灵芝颗粒剂的镇静催眠、增强免疫功能作用。方法：采用开阔法、戊巴比妥钠致小鼠睡眠时间、士的宁致小鼠惊厥法，测定小鼠脾指数、胸腺指数和白细胞数。结果：灵芝颗粒剂能明显减少小鼠自主活动，缩短戊巴比妥钠致小鼠睡眠潜伏期，延长戊巴比妥钠致小鼠睡眠时间，能对抗士的宁致小鼠惊厥的作用，能升高小鼠脾指数、胸腺指数和白细胞数。结论：灵芝颗粒剂具有镇静催眠、增强免疫功能的作用。     

Enhanced Transdermal Delivery of Diazepam by Submicron Emulsion (SME) Creams

Diazepam, a lipophilic drug with CNS activity, serves here as a model to investigate the efficacy of SubMicron Emulsion (SME) as a novel transdermal vehicle. Diazepam was formulated in various topical regular creams and SubMicron Emulsion creams of different compositions. The different formulations were applied topically and protection against Pentamethylenetetrazole induced convulsive effects in mice was monitored. The efficacy of Diazepam applied topically in emulsion creams strongly depends on the oil droplet size and to a lesser degree - on the formulation composition and the oil type. Processing medium-chain-triglyceride (MCT) emulsion with a high-pressure homogenizer causes a drastic reduction in the droplet size, thereby significantly increasing the transdermal activity of Diazepam. In this case both the high-pressure homogenization and the presence of lecithin, an efficient dispersant, contribute to the effective droplet size reduction of below 1 micron, usually between 100–300 nm. The SubMicron Emulsions as vehicles for transdermal delivery of Diazepam generate significant systemic activity of the drug as compared with regular creams or ointments. Transdermal delivery of Diazepam via SME formulations is very effective, and the activity may reach the range of parenteral delivery. A single application of Diazepam in SME cream to mice skin provides pronounced transdermal drug delivery and prolonged protective activity up to 6 hours.     

Blood glucose alterations induced in rats by canatoxin, a protein isolated from jack bean (Canavalia ensiformis) seeds

Canatoxin, a lethal convulsant protein isolated from the seeds of Canatoxin ensiformis (jack bean), induced a biphasic alteration in blood glucose levels when injected i.v. into rats and mice. After administration of subconvulsant doses of canatoxin the rats showed initially hyperglycemia during the first 30 min, followed by a long-lasting hypoglycemia. Return to basal glucose levels was not seen up to 15 days. The hyperglycemic effect was dose-dependent and occurred in starved and well-fed animals. A parallelism between convulsant and hyperglycemic activity was observed throughout all canatoxin purification steps. Mice were about 20-fold less sensitive (on a weight basis) than rats to canatoxin-induced hyperglycemia. The hyperglycemic phase was not affected by pretreatment of the rats with alpha- or beta-adrenergic blockers or chlorpromazine, but was potentiated by reserpine and haloperidol. Diazepam and hexamethonium were able to block the hyperglycemic phase of canatoxin's effect. The results suggest that the hyperglycemic alterations induced by canatoxin in rats and mice are probably mediated via the central nervous system.     

Interactions of pentobarbital and phenobarbital with GABAergic drugs against chemoconvulsants in rats

Pentobarbital and phenobarbital exhibited anticonvulsant effects against picrotoxin (10 mg/kg, IP) as well as against strychnine (4 mg/kg, IP). Pentobarbital was also effective against bicuculline whereas only hypnotic doses of phenobarbital provided some protection against bicuculline- (8 mg/kg, IP) induced convulsions. Diazepam as well as THIP, but not baclofen, were also effective against all the three chemoconvulsants. Baclofen or subeffective doses of diazepam or THIP, but not baclofen, were also effective against all of pentobarbital exhibited anticonvulsant activity against all the chemoconvulsants studied. On the other hand, a combination of subeffective doses of these agents with subeffective doses of phenobarbital provided protection only against picrotoxin and strychnine. These observations indicate that pentobarbital is quite effective against convulsions caused by agents acting at picrotoxin site, GABA_A receptor or glycine receptor whereas phenobarbital is effective only against agents acting at picrotoxin site and glycine receptor, and is very weak anticonvulsant against agents causing blockade of GABA_A receptors. Furthermore, activation of GABA_A receptors or benzodiazepine receptors also provide protection against agents acting at GABAergic system or glycine receptors. On the contrary, activation of only GABA_B receptors is inadequate to provide the protective effect. However, the activation of GABA_A as well as GABA_B receptors facilitate the anticonvulsant effect of both the barbiturates. Furthermore, pentobarbital, but not phenobarbital, facilitates the anticonvulsant effect of benzodiazepines against chemoconvulsants acting at GABAergic site or glycine receptors.     

Coincidence of seizure susceptibility to caffeine and to the benzodiazepine inverse agonist, DMCM, in SWR and CBA inbred mice

Several lines of evidence suggest that the convulsant actions of caffeine are mediated through benzodiazepine receptors. A pharmacogenetic approach has been used to further explore the relationship of these receptors to caffeine-induced seizures. The susceptibility of two inbred strains of mice (CBA and SWR) to the convulsant actions of picrotoxinin, strychnine, Ro 5-4864 and DMCM was examined. Previous studies have demonstrated these two strains differ in their susceptibilities to the convulsant action of caffeine. While no differences were observed between these two strains in susceptibility to tonic seizures induced by picrotoxinin, RO 5-4864 or strychnine, SWR mice were significantly less sensitive to tonic seizures induced by DMCM compared to CBA mice (CD50 values in CBA and SWR mice were 6 and 12 mg/kg IP). Both clonazepam and the benzodiazepine receptor antagonist, Ro 15-1788, significantly blocked caffeine-induced seizures. Further, when subconvulsant doses of caffeine and DMCM were combined, a synergistic action was observed. Taken together, these findings support the hypothesis that the convulsant actions of caffeine result from an action at benzodiazepine receptors, and that the hyporesponsiveness of the SWR strain to both caffeine- and DMCM-induced seizures could result from an inherited abnormality in these sites.     

Possible involvement of the central GABAergic system in pentobarbital-stimulated gastric acid secretion in the perfused rat stomach preparation

The effects of several convulsants and diazepam on pentobarbital-stimulated gastric acid secretion were studied in the perfused stomach of rats under urethane anesthesia. Picrotoxin and pentylenetetrazol, GABA antagonists, and 3-mercaptopropionic acid, an inhibitor of GABA biosynthesis, strongly inhibited the pentobarbital-stimulated gastric acid secretion. The secretory action of pentobarbital was transiently depressed by strychnine, a glycine antagonist, and by bicuculline, a GABA antagonist; vigorous convulsions were observed in these rats. Diazepam had no effect on the pentobarbital-stimulated gastric acid secretion. These findings suggest that the potentiation of central GABAergic mediation by pentobarbital could be a main mechanism involved in pentobarbital-stimulated gastric acid secretion.