妥拉苏林和育亨宾对静松灵及保定宁麻醉羊的催醒实验

通过14只绵羊28次实验,观察到静注妥拉苏林(5mg/kg)可使静松灵(肌注2mg/kg)、保定宁(肌注2mg/kg)麻醉绵羊的平均起立时间(从静注拮抗剂到自行起立行走的时间),由对照的98.6min和95.8min,分别缩短为34.2min和30.4min (P<0.01);静注育亨宾(0.2mg/kg),则分别缩短为65.7min和65.0min(P<0.05)。从而提示,妥拉苏林、育亨宾对静松灵、保定宁麻醉绵羊均有催醒作用,且妥拉苏林优于育亨宾。实验还证明,妥拉苏林和育亨宾对静松灵或保定宁引起的麻醉绵羊的呼吸及心率变化,也有拮抗作用。     

苏醒灵4号、苯恶唑和妥拉苏林对二甲苯胺噻唑麻醉犬催醒作用的研究

麻醉拮抗剂的研究是麻醉技术完善和发展的重要内容,并对麻醉剂作用机制的认识和麻醉药物的发展也具有重要意义.二甲苯胺噻唑(商品名:静松灵)是国内常用的动物麻醉剂.据报道,妥拉苏林等对二甲苯胺噻唑麻醉的犬和绵羊有明显的催醒作用.苯恶唑是高效α_2受体拮抗剂,国外有人报告该药对二甲苯胺噻唑的同类药物Xylazine有明显的拮抗作用.苏醒灵4号是本所新近研制的动物麻醉拮抗剂.本研究比较了上述三种药物     

静松灵对羊瘤胃的影响及α2肾上腺素受体拮抗剂特征的研究

本研究采用胃压测量仪测定静松灵对绵羊胃蠕动的影响，结果如下：α２肾上腺素受体激动剂静松灵可以使羊胃蠕动停止，同等剂量的静松灵比隆朋对羊瘤胃蠕动的副作用大；低剂量（０．１ｍｇ／ｋｇｉｖ）的育亨宾不能显著对抗静松灵，高于０．１ｍｇ／ｋｇ的育亨宾能阻抗静松灵造成的胃蠕动抑制；苯口恶唑有强烈拮抗静松灵的作用，而妥拉苏林的作用弱。     

二甲苯胺噻唑对牛麻醉效果的观察

牛的全身麻醉,过去常应用水合氯醛和酒精,如剂量掌握不好,常引起中毒死亡。二甲苯胺噻唑(又称“静松灵”)是一种麻醉药(分子式:C_(12)H_(10)N_2S),该药具有镇静、镇痛、肌松等作用,以及用量小、作用迅速、应用方便、使用安全等特点。我校于     

氯胺酮与静松灵对雏鸡的麻醉

氯胺酮是一种作用快速的非巴比妥类麻醉药,对大脑中枢的丘脑-新皮质系统产生抑制,镇痛作用较强,但受惊扰仍能醒觉并表现有意识反应[1],苏醒过程不平稳,动物常出现一些兴奋现象[2].静松灵(2,4-二甲苯胺噻唑)为α-2受体激动剂,有安定、镇痛和中枢性肌肉松弛作用[3].     

二甲苯胺噻嗪的作用机制及其拮抗剂的研究现状

二甲苯胺噻唑(静松灵)类药物二甲苯胺噻嗪系2(2,6—二甲苯胺基—4氢—5,6—二氢—1,3—噻嗪的简称,别名有龙朋(rompun)、噻拉嗪(xylazine)等。由德国贝尔公司于1962年首次合成,Sagner等(1968)最先报道了龙朋的药理作用。和静松灵一样,它具有良好的镇痛、镇静和中枢性肌松作用,尤其对反刍兽效果更好。     

妥拉苏林和育享宾对龙朋诱导的绵羊中枢抑制、心动徐缓和呼吸急迫作用的影响

实验用9只母羊和5只公羊比较了妥拉苏林和育享宾对龙朋诱导的中枢神经抑制、心动徐缓及呼吸急迫作用的拮抗能力。每只羊每周实验一次,共三次,即静注龙朋(0.4毫克/公斤)、静注龙朋(0.4毫克/公斤)后10分钟静注安拉苏林(2毫克/公斤)或静注龙朋(0.4毫克/公斤,)后10分钟静注育享宾(0.2毫克/公斤)。随机安排每只羊的实验顺序。单独用龙朋的羊卧地时间为41.0±3.7分钟,妥拉苏林和育享宾可将     

苏醒灵4号的神经药理作用研究

苏醒灵4 号是一种新的复方拮抗剂。本研究旨在探讨其神经药理作用特点。苏醒灵4 号对小鼠自发活动无明显影响,但能拮抗二甲苯胺噻唑对小鼠自发活动的抑制作用;苏醒灵4 号拮抗眠乃宁对小鼠和大鼠的麻醉作用,其作用强度优于同等剂量的苯恶唑;该药对戊巴比妥钠和氯胺酮也有一定的拮抗作用。此外,该药对中枢兴奋剂印防己毒素有微弱的加强作用。总之,苏醒灵4 号本身无明显的药理活性,但能拮抗麻醉剂的中枢抑制作用。     

保定宁的神经药理作用研究

本文对我校军事兽医研究所研制的马属动物全身麻醉药——保定宁的神经药理作用作了研究。试验表明,保定宁(5mg/kg和10mg/kg)对小白鼠自发活动有明显的镇静作用,对电刺激小白鼠所致攻击行为有安定作用,其安定剂量仅为静松灵的1/5～1/10;对用热板法和醋酸法致痛的小白鼠有明显的镇痛作用。保定宁(15mg/kg)还能减少戊四氮,士的宁、苦味毒所致惊厥小鼠的死亡数。这些作用均优于静松灵。保定宁有明显的肌松作用,作用部位在中枢。此作用通过以下几个实验被证实:(1)对雏鸡可产生松弛型麻痹,但这一作用不能为新斯的明所对抗;(2)保定宁对家兔最小垂头量为13.58mg/kg,该量为箭毒最小垂头量(0.37mg/kg)的36倍;(3)对电刺激大自鼠膈神经—膈肌的传递有抑制作用,这一作用仍不能为新斯的明所对抗;(4)对在位兔的胫总神经—胫前肌传递具有部分抑制作用,局部给药时,则出现完全阻滞现象;(5)对在位兔坐骨神经—腓总神经动作电位和坐骨神经—腓肠肌动作电位均有影响,其肌肉动作电位是随着神经动作电位的减小而降低,振幅均由20mv降至10mv,从而证明保定宁对整体动物的神经干传导有部分阻滞作用。但在本试验中,发现保定宁对蟾蜍坐骨神经—缝匠肌终板电位有非常明显的抑制作用,使终板电位的振幅由20mv降至18mv、10mv,直至最后完全     

静松灵拮抗剂——苏醒宁的研制及药效试验报告

静松灵(二甲苯胺噻唑)在兽医临床上已被广泛应用,普遍认为该药具有镇静、肌松和镇痛作用,在实践中也逐渐发现静松灵对机体会产生一些不良作用,如对心脏、呼吸和机体内环境的不良影响[1～3]。本项研究的目的就是要寻找有效的静松灵拮抗剂,即能尽快地消除静松灵麻醉时给机体带     

Antagonistic effects of alpha-adrenoceptor blocking agents on reticuloruminal hypomotility induced by xylazine in cattle.

The intravenous injection of a standard dose (0.05 mg/kg) of xylazine inhibited reticuloruminal motility in cattle. Pretreatment with adrenoceptor antagonists showing alpha 2-blocking activity, tolazoline (0.5 mg/kg) and yohimbine (0.2 mg/kg), antagonized the xylazine-induced reticuloruminal amotility. Tolazoline was more effective than yohimbine, since an antagonistic effect was not seen at 0.5 mg/kg yohimbine, and yohimbine at 0.2 mg/kg was less effective than tolazoline at 0.5 mg/kg. An adrenoceptor antagonist showing alpha 1-blocking activity, prazosin, did not prevent the inhibition of reticuloruminal motility by xylazine. The xylazine-induced reticuloruminal amotility was also not prevented by either a dopamine receptor antagonist, domperidone, or an opiate receptor antagonist, naloxone. These results suggest that xylazine inhibits bovine reticuloruminal motility through its activation of alpha 2-adrenoceptors, and show that tolazoline can be used as a specific antagonist of xylazine in studies of the alpha-adrenergic influence on reticuloruminal motility in cattle.     

静松灵镇痛与脑Ca~(2+)的关系

通过大鼠单侧侧脑室埋管注射和光辐射热甩尾实验,证明静松灵(40mg/kg.sc)具有明显的镇痛作用,CaCl2(1μmol/rat,icv)和EDTA(0.4μmol/rat,icv)分别拮抗和增强静松灵的镇痛作用。异搏定(0.4μmol/rat,icv)和硝苯吡啶(0.4μmol/rat,icv)可增强静松灵的镇痛并可逆转CaCl2对静松灵镇痛的拮抗。脑内5-HT、NE含量与静松灵镇痛密切相关。作者认为,脑Ca2+对静松灵镇痛效应的影响是通过改变脑内NE和5-HT含量而实现的。     

Effects of Brimonidine Ingestion on Cardiovascular Responses and Renal Function in Conscious Dogs

The effects of brimonidine, an α₂-adrenoceptor agonist, on blood pressure, heart rate, respiratory rate, renal function and some blood parameters were investigated in 10 dogs. Dogs were divided into two groups, low dose (LD; 0.2 mg/kg) and high dose (HD; 0.5 mg/kg) of brimonidine given orally. The α₂-adrenergic antagonist yohimbine hydrochloride was injected to dogs at a dose of 0.1 mg/kg in both groups at the fifth hour after brimonidine administration. The results demonstrated that after administration of brimonidine, mean arterial blood pressure decreased dramatically at 2 h by 23% and 20% in LD and HD groups, respectively. Heart rate was decreased in a similar manner and both remained low at 5 h after brimonidine administration. Respiratory rate was decreased by 50%, while the electrocardiogram showed prolongation of the PR interval. Glomerular filtration rate (GFR) and effective renal blood flow were reduced when measured at 4 h after brimonidine ingestion in both groups, but the effect was more pronounced in the LD group. Brimonidine caused natriuresis and kaliuresis in both LD and HD groups. The packed cell volume was decreased and hyperglycaemia was detected. Most of the effects can be reversed completely after administration of yohimbine. However, yohombine can restore GFR only partially. These data suggest that brimonidine caused cardiovascular and respiratory depression. The adverse effects of this drug can be antagonized by yohimbine, suggesting that these effects were mediated via the α₂-adrenoceptor.     

Clinical use of yohimbine as an antagonist of xylazine depression of the central nervous system in cats

Antagonizing effects of various doses of yohimbine on a xylazine depression of the cerebroneural system (CNS) were studied in cats. Administration of various doses of yohimbine was investigated with respect to its antagonizing effects on various doses of xylazine. The time of CNS depression induced by commonly recommended doses of xylazine (2-4 mg/kg live weight) was shortened statistically significantly by intramuscular injections of yohimbine at a dose of 3 mg per kg live weight. After this yohimbine dose, the animals recovered consciousness already 10-15 minutes from application, with the complete resumption of reflexes. Preventive administration of the same dose of yohimbine hindered reliably the full development of CNS depression after the two xylazine doses (2 and 4 mg/kg live weight).     

Reversal of pentobarbital anesthesia with 4-aminopyridine and yohimbine in cats pretreated with acepromazine and xylazine

In 2 separate experiments, groups of atropinized cats (6 cats/group) were given acepromazine (0.25 mg/kg of body weight) or xylazine (2.2 mg/kg) IM and anesthetized with pentobarbital. The mean dose of pentobarbital was decreased approximately 36% by acepromazine, and approximately 80% by xylazine, compared with published doses. Anesthetized cats were given IV saline solution (control groups) or were given the antagonists 4-aminopyridine (4-AP; 0.5 mg/kg), yohimbine (0.4 mg/kg), or 4-AP + yohimbine (0.5 mg/kg and 0.4 mg/kg, respectively). In acepromazine-treated cats, 4-AP + yohimbine was the most effective antagonist; arousal and walking occurred in an average of 10.4 minutes and 91.7 minutes, respectively. Yohimbine enhanced the antagonistic effects of 4-AP. In xylazine-treated cats, yohimbine was an effective antagonist; arousal and walking occurred in an average of 2.8 minutes and 12.8 minutes, respectively. Yohimbine did not enhance the antagonistic effects of 4-AP. Mean respiratory rates were decreased by acepromazine, but were increased by xylazine. Thus, respiratory rate depression by pentobarbital was not as marked with xylazine as it was with acepromazine. Changes in mean heart rate were not remarkable with either sedative, and cardiac irregularities were not palpated or auscultated. In healthy cats, the duration of pentobarbital anesthesia can be controlled by 4-AP + yohimbine (acepromazine-pretreated cats) or by yohimbine alone (xylazine-pretreated cats).     

Clinical evaluation of intranasal benzodiazepines, alpha-agonists and their antagonists in canaries

OBJECTIVE: To evaluate the effects of intranasal benzodiazepines (midazolam and diazepam), alpha(2)-agonists (xylazine and detomidine) and their antagonists (flumazenil and yohimbine) in canaries. STUDY DESIGN: Prospective randomized study. ANIMALS: Twenty-six healthy adult domesticated canaries of both sexes, weighing 18.3 +/- 1.0 g. METHODS: In Study 1 an attempt was made to determine the dose of each drug that allowed treated canaries to be laid in dorsal recumbency for at least 5 minutes, i.e. its effective dose. This involved the evaluation of various doses, during which equal volumes of the tested drug were administered slowly into each nostril. In study 2 the onset of action, duration and quality of sedation induced by each drug at its effective dose were evaluated. The efficacy of flumazenil and yohimbine in antagonizing the effects of the sedative drugs was also studied. RESULTS: In study 1 administration of 25 microL per nostril diazepam (5 mg mL(-1) solution) or midazolam (5 mg mL(-1) solution) to each bird caused adequate sedation within 1-2 minutes; birds did not move when placed in dorsal recumbency. After administration of 12 microL per nostril of either xylazine (20 mg mL(-1)) or detomidine (10 mg mL(-1)), birds seemed heavily sedated and assumed sternal recumbency but could not be placed in dorsal recumbency. Higher doses of xylazine (0.5 mg per nostril) or detomidine (0.25 mg per nostril) prolonged sedation but did not produce dorsal recumbency. In study 2 in all treatment groups, onset of action was rapid. Duration of dorsal recumbency was significantly longer (p < 0.05) with diazepam (38.4 +/- 10.5 minutes) than midazolam (17.1 +/- 2.2 minutes). Intranasal flumazenil (2.5 microg per nostril) significantly reduced recumbency time. Duration of sedation was longer with alpha(2)-agonists compared with benzodiazepines. Detomidine had the longest duration of effect (257.5 +/- 1.5 minutes) and midazolam the shortest (36.9 +/- 2.4 minutes). Nasally administered flumazenil significantly reduced the duration of sedation with diazepam and midazolam while yohimbine (120 microg per nostril) effectively antagonized the effects of xylazine and detomidine. CONCLUSION: Intranasal benzodiazepines produce rapid and effective sedation in canaries. Intranasal alpha(2) agonists produce sedation but not sustained recumbency. Specific antagonists are also effective when used by this route. Clinical relevance Intranasal sedative drug administration is an acceptable alternative method of drug delivery in canaries.     

Effects of tolazoline and yohimbine on xylazine-induced central nervous system depression, bradycardia, and tachypnea in sheep

We compared the ability of tolazoline and yohimbine to antagonize xylazine-induced central nervous system depression, bradycardia, and tachypnea in 9 ewes and 5 rams. Once a week for 3 weeks, each sheep received one IV treatment of 0.4 mg xylazine/kg, 0.4 mg xylazine/kg followed in 10 minutes by 2 mg tolazoline/kg, or 0.4 mg xylazine/kg followed in 10 minutes by 0.2 mg yohimbine/kg. The order of the 3 treatments in each sheep was randomized. Xylazine alone caused recumbency for 41.0 +/- 3.7 minutes (mean +/- SEM). Tolazoline and yohimbine shortened the xylazine-induced recumbency to 12.1 +/- 0.9 minutes and 18.1 +/- 1.5 minutes, respectively. Sheep given xylazine alone had head droop for 34.0 +/- 5.4 minutes after rising. Head drooping of sheep given tolazoline or yohimbine was reduced to 10.1 +/- 1.7 minutes and 14.2 +/- 1.7 minutes, respectively. Both tolazoline and yohimbine reversed the bradycardia and tachypnea that followed xylazine administration. No statistical differences in the rate and magnitude of the reversal were observed between the 2 drugs.     

The effects of jingsongling, a xylazine analog, on mean arterial blood pressure and heart rate in dogs — influences of yohimbine, tolazoline, prazosin, and atropine

The effects of jingsongling (JSL) and xylazine on heart rate (HR) and mean arterial pressure (MAP) were studied in five conscious male dogs. An i.v. injection of xylazine (1 mg/kg) caused a bradycardia, an initial hypertension, and a subsequent hypotension. An i.v. injection of JSL (1 mg/kg) caused a bradycardia and a 20-min hypertension without a subsequent hypotension. Atropine sulfate (45 micrograms/kg, i.v.) increased HR for 30 min without changing MAP, and antagonized JSL-induced bradycardia for at least 60 min. There was a subsequent rebound bradycardia. Atropine sulfate potentiated JSL-induced hypertension in both magnitude and duration. Yohimbine (0.1 mg/kg, i.v.), an alpha 2-adrenoceptor antagonist, increased HR and MAP for 110 and 70 min, respectively. Yohimbine not only failed to potentiate but even reversed the pressor effect of JSL in a dose-dependent manner. Yohimbine also caused a dose-dependent reversal of JSL-induced bradycardia. Tolazoline (5 mg/kg, i.v.), a nonselective alpha-adrenoceptor antagonist, increased MAP for 20 min without changing HR. Tolazoline also reversed JSL-induced hypertension and bradycardia. Prazosin (1 mg/kg), an alpha 1-adrenoceptor antagonist, decreased MAP and increased HR for at least 110 min. Prazosin reversed JSL-induced hypertension but failed to affect JSL-induced bradycardia. These results indicated that: (1) JSL-induced bradycardia and hypertension are mediated by alpha 2-adrenoceptors; (2) yohimbine and tolazoline may be useful in antagonizing these untoward reactions associated with JSL administration, whereas prazosin and atropine were not found to be beneficial in this regard.     

Evaluation of Three Midazolam-Xylazine Mixtures Preliminary Trials in Dogs

The depressant effects of midazolam and xylazine on the central nervous system (CNS) were evaluated in 12 dogs. Xylazine was administered to six dogs (1.1 mg/kg intravenously [IV]) followed in 5 minutes by midazolam (1.0 mg/kg intramuscularly [IM]). In a second group of six dogs, xylazine (2.2 mg/kg IM) was followed in 5 minutes by midazolam (1.0 mg/kg IV). Both drug regimens induced rapid and profound sedation or anesthesia. Duration of action varied with the doses and routes of administration. Dogs given the high dose of xylazine IM had an arousal time of 95.4 +/- 8.9 minutes and a walking time of 155.4 +/- 8.8 minutes. These values exceeded the IV xylazine values threefold. Partial reversal of CNS depression was accomplished with either a benzodiazepine antagonist (flumazenil) or an alpha-2 antagonist (yohimbine). In a separate trial, a mixture of xylazine (0.55 mg/kg), midazolam (1.0 mg/kg), and butorphanol (0.1 mg/kg) with and without glycopyrrolate was evaluated in eight dogs. As with the xylazine-midazolam combinations, the CNS depressant effect of this mixture was clinically indistinguishable from anesthesia achieved with other rapid-acting injectable agents. Clinical signs of CNS depression were readily and completely antagonized by the simultaneous injection of flumazenil and yohimbine.     

Influence of yohimbine and tolazoline on the cardiovascular, respiratory, and sedative effects of xylazine in the horse

To determine the effects of yohimbine and tolazoline on the cardiovascular, respiratory and sedative effects of xylazine, four horses were sedated with xylazine and treated with either yohimbine, tolazoline or saline. Xylazine was administered as an intravenous (i.v.) bolus (1.0 nig/kg) followed by a continuous infusion at the rate of 12 μg/kg/min. Heart rate, respiratory rate, mean arterial pressure, arterial blood gases, and the chin-to-floor distance were recorded throughout the experiment. After 60 min, either yohimbine or tolazoline was administered i.v. in incremental doses until reversal of sedation (defined as the return of the chin-to-floor distance to baseline values) was achieved. A control group in which a saline bolus was administered instead of an antagonist drug was included for comparison.
The average dose of yohimbine administered was 0.12 ± 0.02 (SEM) mg/kg. While the average dose of tolazoline was 7.5 ± 1.1 mg/kg. Both tolazoline and yohimbine antagonized the ventricular bradycardia and A-V conduction disturbances observed with xylazine administration. No change in mean arterial pressure was observed with xylazine or yohimbine administration, but tolazoline caused persistent mild systemic hypertension. There were no clinically significant changes in respiratory rate or arterial blood gas values with administration of either xylazine, yohimbine or tolazoline. The chin-to-floor distance decreased significantly with xylazine administration and increased significantly with administration of either yohimbine or tolazoline. In conclusion, both yohimbine and tolazoline successfully antagonized the cardiovascular and CNS depression associated with xylazine administration.