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阿片类药物、心境稳定剂和多巴胺能药物对毛果芸香碱诱发癫痫发作和癫痫持续状态的药理学研究。

Pharmacological studies of the opioids, mood stabilizer and dopaminergic drugs on pilocarpine-induced seizures and status epilepticus.

作者信息

Freitas R M, Vasconcelos S M M, Sousa F C F, Viana G S B, Fonteles M M F

机构信息

Department of Physiology and Pharmacology, Laboratory of Neuropharmacology, School of Medicine, Federal University of Ceara, Rua Cel. Nunes de Melo 1127, Fortaleza 60431-970, CE, Brazil.

出版信息

Neurosci Lett. 2006 Nov 13;408(2):84-8. doi: 10.1016/j.neulet.2006.08.009. Epub 2006 Sep 29.

Abstract

This work was designed to study the influence of drugs during seizures and status epilepticus (SE) induced by pilocarpine and mortality in adult rats. Morphine (0.1 and 0.2 mg/kg), SCH 23390 (0.1 and 0.2 mg/kg), haloperidol (5 and 10mg/kg) and lithium (30 and 60 mg/kg) were administered intraperitoneally (i.p.), 30 min before to pilocarpine (400 mg/kg, s.c.). The animals were observed (24 h) to determine: number of peripheral cholinergic signs, tremors, stereotyped movements, seizures, SE, latency to first seizure and number of deaths after pilocarpine treatment. Morphine and haloperidol had proconvulsant effects in both doses tested. Smaller and higher doses of these drugs no protected and increased pilocarpine-induced seizures, SE and/or mortality. SCH 23390 protected against seizures, increased the latency to first seizure and reduced the mortality of the animals treated with pilocarpine Theses results suggest that dopamine receptor system receptor subtypes exert opposite functions on the regulation of convulsive activity. The morphine is proconvulsant in lower doses. The opioids in high doses tested exert an action proconvulsant during the establishment of epileptic activity induce by pilocarpine. The lithium no protected the animals against seizures induced by pilocarpine and is used which a model of epilepsy associated with lower doses of pilocarpine in several studies, suggesting absence of the effect anticonvulsants in rodents.

摘要

本研究旨在探讨药物对毛果芸香碱诱导的成年大鼠癫痫发作和癫痫持续状态(SE)的影响以及死亡率。在腹腔注射毛果芸香碱(400mg/kg,皮下注射)前30分钟,腹腔注射吗啡(0.1和0.2mg/kg)、SCH 23390(0.1和0.2mg/kg)、氟哌啶醇(5和10mg/kg)和锂(30和60mg/kg)。观察动物24小时,以确定:外周胆碱能体征数量、震颤、刻板运动、癫痫发作、SE、首次癫痫发作潜伏期以及毛果芸香碱治疗后的死亡数量。吗啡和氟哌啶醇在两种测试剂量下均有惊厥作用。这些药物的较小和较高剂量均未起到保护作用,反而增加了毛果芸香碱诱导的癫痫发作、SE和/或死亡率。SCH 23390可预防癫痫发作,延长首次癫痫发作潜伏期,并降低毛果芸香碱治疗动物的死亡率。这些结果表明,多巴胺受体系统受体亚型在惊厥活动调节中发挥相反作用。低剂量吗啡具有惊厥作用。在高剂量测试中,阿片类药物在毛果芸香碱诱导的癫痫活动建立过程中发挥惊厥作用。锂不能保护动物免受毛果芸香碱诱导的癫痫发作影响,并且在多项研究中,锂与较低剂量的毛果芸香碱一起用于癫痫模型,这表明在啮齿动物中不存在抗惊厥作用。

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