二甲苯胺噻唑在绵羊血液中的药物动力学研究

给绵羊肌注二甲苯胺噻唑（２．５ｍｇ／ｋｇ）用内标气相色谱法测出其不同时间的血药浓度，药动学分析结果表明，血药经时特征主要符合一级吸收单室开放模型，部分符合一级吸收双室开放模型．其主要药动学参数：吸收半衰期为９．２８２±２．５７９ｍｉｎ，消除半衰期为８１．０６９±３０．６３１ｍｉｎ，达峰时间为２９．１２０±５．７７１ｍｉｎ，峰浓度为０．２７０５±０．１３０９μｇ／ｍｌ，药时曲线下面积为３０．５３２±１１．５００８μｇ／ｍｌ·ｍｉｎ．     

二甲苯胺噻唑对绵羊肌电图影响的研究

以日产３６２型多道生理仪为主要手段，研究了静松灵对绵羊的肌肉系统的作用。实验结果表明，静松灵对肌肉产生良好的肌松作用，肌电图表现为肌电活动明显减少和振幅度降低等，肌松作用大约持续１小时。     

二甲苯胺噻唑对绵羊心电图影响的研究

研究了静松灵对绵羊的心脏传导系统的作用，实验结果表明，静松灵对心脏系统产生较生时间的抑制作用，心电图表现为第１，１１度房室传导阻滞、窦性心动徐缓、窦性心律不齐和抑制心室的复极过程等，而对心室内的传导却无明显的影响，静松灵对心脏的抑制作用从给药后５分钟，持续几个小时。     

二甲苯胺噻唑在绵羊脑脊液中的药物动力学研究

以内标气相色谱法为定量手段，研究二甲苯胺噻唑在绵羊脑脊液（ＣＳＦ）中的药动力学。实验结果表明，绵羊肌注二甲苯胺噻唑（２．５ｍｇ／ｍｌ）后，ＣＳＦ药物经时特征主要符合一级吸收单室开放模型，部分符合一级吸收双室开放模型，其主要药动学参数：吸收半衰期为３．８６８±１．４５２ｍｉｎ，消除半衰期为１４０．３３８±１１０．０３８ｍｉｎ，ＣＳＦ药浓度达峰时间为１７．６３７±５．８５０ｍｉｎ，ＣＳＦ药峰浓度为０．     

二甲苯胺噻唑对犬麻醉效果的观察研究

将２５条健康成年犬，不分品种、性别、毛色，随机分成５组，每组５条。麻醉前，先检测各项生理指标和痛阈值，然后每组犬分别按不同剂量肌肉注射２％二甲苯噻唑，给药后间隔不同时间观测麻醉效果，结果表明：所有用药犬均出现镇静、镇痛、肌松的现象，随药量的增大，麻醉效果加深，苏醒时间延长，但未出现死亡或其他意外事故。     

二甲苯胺噻唑有关物质检查方法探讨

二甲苯胺噻唑（静松灵）是化学保定药,有镇静、镇痛和肌肉松弛作用,在兽医临床上得到广泛的应用。该药品现行质量标准（《兽药规范》１９９２年版一部）中未规定有关物质的检查项［１］,考虑到本品在合成过程中易引入杂质,为控制杂质限量并提高产品质量,作者等对二甲苯胺噻唑有关物质的检查进行了探索。１　实验条件薄层板用硅胶ＧＦ２５４自制板,厚度为５００μｍ;显色为置紫外灯下（２５４ｎｍ）检视;展开方式为上行展开。供试液制备：１＃：取二甲苯胺噻唑粗品,加无水乙醇制成每１ｍｌ含２５ｍｇ的溶液;２＃：取二甲苯胺噻嗪,…     

二甲苯胺噻唑神经药理作用的研究

本实验对二甲苯胺噻唑(静松灵)的镇静、镇痛、肌松、安定和抗惊厥等中枢抑制作用进行了较为系统的研究;观察了该药对大鼠自发性脑电变化的影响;对该药的作用机理作了初步探讨。结果:(1)二甲苯胺噻唑具有良好的镇静、镇痛和松肌作用,较大剂量有一定的安定作用,但安全性差;(2)对戍四氮、士的宁和苦味毒所致惊厥反应无对抗作用;(3)对神经于神经冲动的传导具有阻断效应,(4)可诱导大鼠脑电出现高幅慢波,惊醒反应消失,妥拉苏林和育亨宾对此有拮抗作用;(5)妥拉苏林和育亨宾对二甲苯胺噻唑制动大有催醒作用,且可缓解该药的中毒反应。结果提示,中枢性α_2—肾上腺素能受体参与了二甲苯胺噻唑中枢抑制作用的产生过程。     

二甲苯胺噻唑在羊、兔体内的药动-药效同步模型的研究

以气相色谱（ＧＣ）、高效液相色谱（ＨＰＬＣ）、荧光分析与放射免疫（ＰＩＡ）等方法为检测手段,提供药动学数据;以脑电、心电、肌电等数据作药效学定量指标,经计算机拟合后,获得二甲苯胺噻唑（ＸＬ）的药动－药效（ＰＫ－ＰＤ）同步模型参数。血药动力学与脑电拟合同步模型参数为Ｎ（Ｈｉｌｌ系数）＝０．１０１２３,ｋｅｏ（效应室消除速率常数）＝０．２２０９ｍｉｎ＾－１,ｔ１／２ｋｅｏ（血药浓度－药效平衡半衰期）＝     

二甲苯胺噻唑的作用机制

二甲苯胺噻唑是中国农科院 1974年研制成功的一种新型兽用化学保定药 ,商品名为“静松灵”。目前认为二甲苯胺噻唑具有镇静、镇痛及中枢性肌肉松驰作用 ,同时具有一些临床副作用 ,包括 :心动过缓 ,血压下降 ,反刍减弱 ,呕吐 ,胃臌气以及呼吸次数下降等。许多学者对其作用机制进行了广泛而深入的研究 ,初步认定本品是二甲苯胺噻嗪 (隆朋 )的类似物 ,是一种α2 肾上腺受体 (简称α2 受体 )激动剂 ,并对化学递质去甲肾上腺素 (ＮＥ) ,乙酰胆碱 (Ａｃｈ)及 β—内啡肽 (β—Ｅｐ)有显著影响[1] 。1　二甲苯胺噻唑的中枢抑制机理1.1　α2 受体与…     

赛拉唑对大鼠不同脑区NO-NOS-cGMP信号转导系统的影响

观察赛拉唑对大鼠不同脑区NOS活性、NO和cGMP含量的影响,以探讨NO-NOS-cGMP信号转导系统对赛拉唑全麻分子机理的调控.Wistar纯种大鼠84只,随机选取12只为生理盐水对照组,其余随机均分为低剂量赛拉唑用药组和高剂量赛拉唑用药组,每个剂量组又分为麻醉期、翻正反射恢复期和苏醒期3个亚组(各12只).用分光光度法测定大鼠不同脑区NOS活性和NO产量,放射免疫法测定脑cGMP含量.结果表明,赛拉唑能明显地抑制大鼠大脑皮质、小脑、海马和脑干NOS活性、NO和cGMP含量.并且NOS活性、NO含量的抑制作用呈现荆量依赖性增加趋势,这种变化与大鼠赛拉唑麻醉后行为学变化相吻合.结果提示,NO-NOS-cGMP信号传递系统参与了赛拉唑全麻作用产生的分子学机制的调控.     

Effects of xylazole alone and in combination with ketamine on the metabolic and neurohumoral responses in healthy dogs

ObjectiveTo evaluate the effects of xylazole (an analogue of xylazine), also known as Jingsongling, alone and in combination with ketamine, on metabolic and neurohumoral responses in healthy dogs.Study designProspective randomized experimental study.AnimalsTwelve healthy mongrel dogs (7 male, 5 female, aged 13–20 months, weighing 12.8–15.4 kg).MethodsEach dog received one of two treatments: xylazole 4 mg kg^?1 (group X n = 6); or xylazole 4 mg kg^?1 plus ketamine 10 mg kg^?1 (group XK; n = 6) intramuscularly. Pulse rate (PR), mean arterial pressure (MAP), respiratory rate (f_R), and rectal temperature (RT) were recorded before and from 5 to 100 minutes after drug administration. Venous blood samples were taken before and at intervals from 0.5 to 24 hours after drug administration for determination of plasma concentrations of norepinephrine, epinephrine, β–endorphin, cortisol, insulin, and glucose. Statistical analyses employed anova for repeated measures for changes with time and anova for comparison between treatments.ResultsIn both treatment groups. PR, f_R and RT decreased. MAP increased transiently. At some time points PR, MAP and RT were significantly lower in group X than group XK. Plasma norepinephrine, epinephrine, and insulin concentrations decreased, and β–endorphin and glucose concentrations increased with both treatments. Higher values of plasma norepinephrine, epinephrine, β–endorphin, and glucose concentrations were observed in the XK group compared with the X group.Conclusions and clinical relevanceThis study demonstrates that xylazole administered alone or in combination with ketamine in healthy dogs results in physiological, metabolic and neurohumoral responses similar to those seen after xylazine. Compared with xylazole alone, the combination of xylazole and ketamine reduced some of the responses.     

Cerebrospinal fluid from a dog with hind limb ataxia

A 9-year-old spayed female German Shepherd dog with a history of orthopedic disease was presented to the North Carolina State University Veterinary Teaching Hospital for evaluation of recent, progressive, bilateral, hindlimb ataxia. Analysis of cisternal and lumbar cerebrospinal fluid (CSF) samples revealed normal total nucleated cell counts and a mild increase in protein concentration in the lumbar sample. In cytocentrifuged specimens of both CSF samples, aggregates of refractile, angular to irregular, pale blue to colorless, crystalline material were observed in the background. Some of the material appeared birefringent under polarized light. Differentials for the material included contrast agent, epidural anesthetics or other pharmacologic agents, or artifact introduced through sample processing, collection, or handling. Based on investigation of clinical and laboratory processes it was determined that tubes used to collect CSF in the hospital recently had been changed from additive-free glass tubes to silica-coated shatter-resistant plastic tubes (BD Vacutainer Plus serum tubes, silicone-coated, Becton Dickinson). A cytocentrifuged preparation of saline placed in a silica-coated tube contained crystalline material identical to that observed in the CSF samples; saline placed in an additive-free glass tube contained no material. In this case, we document the microscopic appearance of highly concentrated silica particles in cytocentrifuged preparations of CSF and underscore the importance of recognizing and identifying this artifact in cytologic preparations.     

犬正常脑脊液及脊髓造影时压力波的动态变化研究

用生理多导仪分别记录麻醉状态下正常犬脑脊液压力(CSFP)和麻醉状态下蛛网膜下腔注射造影剂时CSFP、呼吸和心跳的动态变化。发现CSFP受呼吸影响较大，一呼一吸为CSFP波的1个周期。其次，心跳也对波形产生影响。比较2种条件下的CSFP波，发现蛛网膜下腔注射造影剂可引起CSFP显著升高，且变化幅度显著增大。     

Cerebrospinal fluid analysis and magnetic resonance imaging in the diagnosis of neurologic disease in dogs: a retrospective study

BACKGROUND: Diagnosis of central nervous system (CNS) abnormalities in dogs can be challenging antemortem. Historically, cerebrospinal fluid (CSF) analysis has been used for routine diagnostic evaluation of animals with suspected neurologic disease; however, with increasing availability of magnetic resonance (MR) imaging, the need for concurrent CSF analysis may be questioned. OBJECTIVE: The purpose of this study was to retrospectively assess and compare the diagnostic information contributed from MR imaging and CSF analysis in a population of dogs presenting with neurologic disease. METHODS: Results of concurrent MR imaging and CSF analysis were evaluated in dogs presented for neurologic diseases. Based on clinical diagnosis, the sensitivity of CSF analysis and MR imaging for detecting a nervous system abnormality was calculated. Dogs with diagnoses confirmed by other diagnostic modalities were also evaluated separately. RESULTS: A total of 256 dogs were included in the study. For clinical diagnoses in which abnormalities were expected, MR imaging abnormalities were found in 89% and CSF abnormalities in 75% of dogs; CSF abnormalities were more common than MR imaging abnormalities only in inflammatory CNS disease. The majority of CSF abnormalities were nonspecific; an etiologic diagnosis was determined in only 2% of CSF samples. MR imaging excelled in detecting structural disorders, revealing 98% of vertebral abnormalities. In confirmed cases (n = 55), 76% of MR images and 9% of CSF samples were diagnostic. When intervertebral disk disease (IVDD) and vertebral malformation were excluded from analysis (n = 16 remaining), 25% of MR images and 6% of CSF cytology results were highly indicative of the confirmed diagnoses; CSF titer results provided the diagnosis in 25% of these cases. CONCLUSION: CSF analysis may not be necessary when MR findings of IVDD or vertebral malformation/instability are obvious; however, when the cause of neurologic disorder is uncertain, concurrent MR imaging and CSF analysis provides the greatest assistance in establishing a clinical diagnosis.     

Concentrations of vatinoxan and xylazine in plasma,cerebrospinal fluid and brain tissue following intravenous administration in sheep

ObjectivesTo investigate the extent of vatinoxan distribution into sheep brain, and whether vatinoxan influences brain concentrations of xylazine; and to examine the utility of cerebrospinal fluid (CSF) as a surrogate of brain tissue concentrations for vatinoxan and xylazine.Study designRandomised, blinded, experimental study.AnimalsA total of 14 adult female sheep.MethodsSheep were randomly allocated into two equal groups and premedicated with either intravenous (IV) vatinoxan (750 μg kg^–1, VX) or saline (SX) administered 10 minutes before IV xylazine (500 μg kg^–1). Sedation was subjectively assessed at selected intervals before and after treatments. At 10 minutes after xylazine administration, a venous blood sample was collected and the sheep were immediately euthanised with IV pentobarbital (100 mg kg^–1). Plasma, CSF and brain tissues were harvested, and concentrations of vatinoxan and xylazine were quantified using liquid chromatography–tandem mass spectrometry. Drug ratios were then calculated and the data were analysed as appropriate.ResultsThe brain-to-plasma and CSF-to-plasma ratios of vatinoxan were 0.06 ± 0.013 and 0.05 ± 0.01 (mean ± standard deviation), respectively. Xylazine brain concentrations were not significantly different (835 ± 262 versus 1029 ± 297 ng g^–1 in groups VX and SX, respectively) and were approximately 15-fold higher than those in plasma. The CSF-to-brain ratio of vatinoxan was 0.8 ± 0.2, whereas xylazine concentrations in the brain were approximately 17-fold greater than those in CSF, with and without vatinoxan.Conclusions and clinical relevanceVatinoxan did not significantly affect sedation with xylazine or the concentrations of xylazine in the brain. CSF is not a good predictor of xylazine concentrations in the brain, whereas vatinoxan concentrations were concordant between the brain and CSF, using the dosages in this study.