纳络酮合成法的改良

纳络酮是吗啡类药物中毒的特效解毒剂,也是研究脑神经介质功能的重要工具药物。一般是采用蒂巴因为原料,经氧化,还原制成14-羟基7,8-二氢可待因酮Ⅰ后,与盐酸吡啶或三溴化硼反应将3-位甲醚基的甲基裂去,制成14-羟基7,8-二氢吗啡酮Ⅱ,经酰化制得Ⅲ,氰化制成Ⅳ,水解制成14-羟基7,8-二氢降吗啡酮Ⅴ,再经烯丙基化制成纳络酮Ⅵ。由于(Ⅰ)具有3-甲氧基和氧环两个醚基,在制备Ⅱ时采用选择性较高的试剂三溴化硼收率较     

长效镇痛药14-羟基可待因酮和14-羟基吗啡酮腙类衍生物的合成

14-羟基二氢可待因酮(Oxycodone Ia)和14-羟基二氢吗啡酮(oxymorphinone)均为有效的镇痛药。最近Pasternak等报道14-羟基二氢吗啡酮腙(Ⅱa)为鸦片受体的不可逆结合激动剂,具有长效药理作用。我们曾合成了此化合物,发现它很不稳定,在乙醇溶液中放置后即分解,这与纳络酮与肼缩合制备纳络酮腙(Ⅱb)时为可逆反应的报道一致。为了增     

6β-纳曲醇与纳曲酮拮抗吗啡镇痛作用的比较6β-纳曲醇与纳曲酮拮抗吗啡镇痛作用的比较

目的比较6β-纳曲醇(6β-naltrexol,6β-NOL)与纳曲酮(naltrexone,NTX)拮抗吗啡的镇痛作用。方法用小鼠热板法和小鼠热辐射甩尾法,sc和ig两种途径研究6β-NOL和NTX拮抗吗啡镇痛作用的强度和有效时间。用放射配体结合实验研究6β-NOL和NTX对阿片受体的亲和力。结果小鼠热板法和甩尾法显示,6β-NOL的抗吗啡镇痛作用强度和有效时间分别约为NTX的(6.1±1.7)%和3～4倍;po拮抗吗啡镇痛作用强度约为sc的30%,与NTX相近。在受体水平,6β-NOL对阿片-mu受体的亲和力约为NTX的12.5%,这与它们在整体水平拮抗吗啡镇痛作用的强度相近。结论6β-NOL抗吗啡镇痛作用比NTX弱,但作用时间长。     

不同止呕药预防妇科术后硬膜外吗啡镇痛后恶心呕吐的临床观察

目的观察比较小剂量地塞米松与恩丹西酮用于妇科良性手术患者术后硬膜外吗啡镇痛的恶心呕吐的预防作用.方法随机双盲选择90例在硬膜外麻醉下行妇科良性手术患者进行观察,所有患者在手术后均接受硬膜外吗啡镇痛.在予镇痛首剂前10分钟分别给对照组(C组n=30)生理盐水10 ml,恩丹西酮组(0组n=30)恩丹西酮8mg,地塞米松组(D组n=30)地塞米松10mg.结果在手术后48小时内,C组恶心发生率为1 3%,呕吐发生率为30%,而0组相应为6.67%、和3.3%,D组相应为6.67%,6.67%,前24小时和后24小时均无明显差异.结论小剂量地塞米松和恩丹西酮均能有效地预防妇科硬膜外吗啡镇痛在镇痛期内引起的呕吐.     

滇西嘟拉碱甲的镇痛和身体依赖性研究

用扭体法、热板法、光热-甩尾法和甲醛致痛法证实Bul有明显镇痛作用。连续给药9 d,镇痛作用无耐受现象。小鼠跳跃反应试验阴性;Bul对吗啡依赖大鼠或猴的戒断症状,均无替代作用。Bul的镇痛作用不能被纳络酮翻转;利血平可取消Bul的镇痛作用,补充5-HT或5-HTP能翻转利血平取消Bul的镇痛作用。     

纳曲酮与纳洛酮对吗啡,依托尼秦及羟甲芬太尼的拮抗作用…

在整体和受体水平对阿片受体拮抗剂的纳曲酮和纳洛酮对吗啡，依托尼秦和「＾３Ｈ」羟甲芬太尼的拮抗作用进行了比较。研究表明，在整体水平，纳曲酮在很小剂量下就能对抗吗啡在小鼠的镇痛作用，小鼠吗啡急性中毒以及依托尼秦致大鼠翻正反射消失。     

羟考酮的镇痛及依赖的实验研究进展

羟考酮（oxycodone）又称14-羟基二氢可待因酮、羟可酮、氧可酮。其化学式为4，5-还氧基-14-羟基-3-甲氧基吗啡烷-6-酮。是阿片类生物碱蒂巴因（thebaine）的衍生物。羟考酮在临床应用有80多年的历史。首先在美国羟考酮与非阿片类药物的复方制剂口服用于治疗中、重度癌性和非癌性疼痛。大量临床试验证明，单一制剂羟考酮，可控制非阿片类药物与羟考酮、或吗啡的复方制剂无法缓解的中、重度癌性和非癌性疼痛。目前在我国已有羟考酮的产品进入市场。本文将系统的综述羟考酮的镇痛及其依赖的实验研究进展。     

6β-纳曲醇与纳曲酮拮抗吗啡镇痛作用的比较

目的　比较 6 β 纳曲醇 ( 6 β naltrexol,6 β NOL)与纳曲酮 (naltrexone ,NTX)拮抗吗啡的镇痛作用。 方法　用小鼠热板法和小鼠热辐射甩尾法 ,sc和ig两种途径研究 6 β NOL和NTX拮抗吗啡镇痛作用的强度和有效时间。用放射配体结合实验研究 6 β NOL和NTX对阿片受体的亲和力。 结果　小鼠热板法和甩尾法显示 ,6 β NOL的抗吗啡镇痛作用强度和有效时间分别约为NTX的 ( 6 1± 1 7) %和 3～ 4倍 ;po拮抗吗啡镇痛作用强度约为sc的 30 % ,与NTX相近。在受体水平 ,6 β NOL对阿片 mu受体的亲和力约为NTX的 12 5 % ,这与它们在整体水平拮抗吗啡镇痛作用的强度相近。结论　 6 β NOL抗吗啡镇痛作用比NTX弱 ,但作用时间长     

吗啡与芬太尼联合应用对术后镇痛效果影响的研究

目的观察吗啡与芬太尼联合对患者对术后镇痛效果的影响。方法择期肺癌手术患者90例,ASAI-II级,全身麻醉术前30min,静脉接镇痛泵,A组镇痛泵药液为吗啡0.05mg/（kg·d）,芬太尼4μg/（kg·d）,恩丹西酮0.08mg/（kg·d）,B组镇痛泵药液为吗啡0.1mg/（kg·d）,恩丹西酮0.08mg/（kg·d）,C组镇痛泵药液为芬太尼8μg/（kg·d）,恩丹西酮0.08mg/（kg·d）,3组均用0.9%生理盐水稀释至100ml,注入速度2ml/h。术后根据患者的疼痛情况,VAS评分5分以上者肌内注射哌替啶50-100mg镇痛。三组患者均于术后6、24、48h观察疼痛评分（VAS）;镇静评分;镇痛期间的不良反应：恶心、呕吐、呼吸抑制、低血压等;镇痛效果的满意程度。结论A组的VAS评分低于B、C两组（P〈0.05）,B、C两组的镇静评分明显比A组高（P〈0.01）。在术后镇痛期间恶心A组低于B、C两组（P〈0.05）,均未发生呕吐、呼吸抑制等其他不良反应。镇痛结束后A组患者对镇痛效果的满意度显著优于B、C组（P〈0.05）。结论吗啡-芬太尼-恩丹西酮经静脉联合应用进行术后镇痛镇痛效果确切,不良反应小,已能达到胸科开胸手术患者术后有效镇痛的基本要求。     

维生素K_3中枢镇痛效应的探讨

经由大鼠、小鼠甩尾及兔甩头法测痛,证实k_3具有剂量依赖的镇痛作用。兔侧脑室微量注射k_3亦有显著镇痛效应。k_3的镇痛作用可被阿片拮抗剂纳络酮所拮抗。实验观察到k_3与吗啡的镇痛效应间存在交叉耐受现象。一定浓度的k_3可抑制电场刺激所致豚鼠回肠纵肌标本的收缩,这一效应亦可被纳络酮部分逆转。小鼠经k_3预处理后对k_3的镇痛产生耐受;连续k_3大剂量预处理后纳络酮激发不产生跳跃。     

Effect of citalopram and buspirone on the antinociceptive action of analgesic drugs.

The influence of citalopram (20 mg/kg i.p.) and buspirone (3 mg/kg i.p.) on analgesic effects of morphine (10 mg/kg i.p.), metamizole (500 mg/kg i.p.) and indomethacin (10 mg/kg) was studied with tail-flick and hot-plate tests on mice. The research studies were further conducted with multiple (14 days) drug dosage. The results indicate that citalopram and buspirone decrease analgesic effects of morphine, metamizole and indomethacin. This mode of action is more pronounced in case of a single dose than after multiple doses.     

延胡索的药理研究(Ⅳ)延胡索素乙和丑对循环和呼吸的影响

1.給麻醉猫靜脉內慢慢注射延胡索素乙40毫克/千克(相当2倍鎮痛有效剂量)时,血压略降,心跳变慢,心脏功能無明显变化.正常家兔靜脉注射乙素20或40毫克/千克时,呼吸短时兴奋;剂量增至60毫克/千克(相当3倍鎮痛有效剂量)时,呼吸有抑制. 2.麻醉猫靜脉內慢慢注射延胡索素丑30毫克/千克(相当鎮痛有效剂量的2倍),血压略降,心跳变慢,心电圖的T波有倒置現象。正常家兎靜脉注射丑素30毫克/千克时,对呼吸無抑制,而有兴奋現象。     

General pharmacological studies on 5,8,11,14,17-eicosapentaenoic acid ethyl ester (EPA-E)

EPA-E, even at 3,000 mg/kg, p.o., did not affect the general behaviors, spontaneous locomotor activities, pentobarbital hypnosis and body temperature; and it did not elicit anticonvulsant, analgesic and muscle relaxant actions. It had no influence on spontaneous EEG activities, even at 3,000 mg/kg, i.d. EPA-E at concentrations up to 10(-4) M, did not affect the tonus or agonist-induced contraction of the isolated ileum, trachea, fundus and vas deferens. EPA-E had no influence on the spontaneous movement of isolated ileum or uterus. EPA-E did not affect the nictitating membrane contraction and intestinal propulsive motility, and it did not damage gastric mucosa nor elicit antiulcer action. EPA-E at 1,000 mg/kg were without effect on gastric secretory volume (SV), total acidity (TA) and pepsin activities (PA). However, EPA-E at 3,000 mg/kg significantly decreased SV and TA without significantly decreasing PA. EPA-E caused no changes in the respiration, blood pressure, heart rate and ECG at the doses up to 3,000 mg/kg; and it did not affect the heart rate and contractile force on the isolated atria at concentrations up to 10(-4) M. The intracutaneous injection of 2.0% EPA-E produced neither anesthetic nor irritative action. EPA-E did not elicit hemolytic action at 10(-4) M. EPA-E, even at 3,000 mg/kg, did not affect the neuro-muscular transmission, urine volume, urinary excretion of electrolytes and carrageenin edema. These results suggested that EPA-E has no noticeable effects on the central nervous, autonomic nervous, respiratory and cardiovascular systems and so on.     

肌肉注射曲马多对老年患者开胸术后镇痛的疗效观察

目的 :观察肌肉注射曲马多对老年患者开胸术后疼痛的疗效及安全性。方法 :对34例开胸术后中、重度疼痛的老年患者肌肉注射曲马多1 5mg/kg ,观察即时镇痛效应及不良反应情况。结果 :显效率41 2 % ,总有效率可达79 4 % ;有一过性恶心、呕吐、出汗、排尿困难等不良反应 ,无1例出现呼吸抑制。结论 :老年患者开胸术后肌肉注射曲马多是安全、有效的镇痛措施     

General pharmacology of DW-286a, a new fluoronaphthyridone antibiotic: effects on central nervous, cardiovascular, and respiratory systems

DW-286a is a new class of fluoronaphthyridone antibiotic. Its effect on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied. The doses given were 30, 50, 100, 150, 300, and 1000 mg/kg and drugs were administered orally. DW-286a did not show any effects on general behavior, motor coordination, analgesic action, seizure and mortality, blood pressure and heart rate, contractile response of isolated guinea pig ileums, and renal function. On the other hand, DW-286a decreased spontaneous locomotor activity from 120 to 240 min after administration at the doses of 300 and 1000 mg/kg and the respiration rate from 30 to 240 min after the administration of doses up to 100 mg/kg. The sleeping time and body temperature were increased significantly in mice at the dose of 1000 mg/kg. DW-286a increased the charcoal transport significantly at doses of 300 and 1000 mg/kg. DW-286a inhibited gastric acid secretion, reduced the volume of the gastric juice and total acidity, and increased the pH dose dependently. Based on the above results, it was concluded that DW-286a affects spontaneous locomotor activity, respiration and body temperature, gastrointestinal transport, gastric secretory action, and hexobarbital sleeping time at high doses.     

吲哚拉新(Indolacin)的药理研究

吲哚拉新灌胃给药,对角叉菜胶所致大鼠踝关节肿胀具有抑制作用,其 ED_(50)为11.6±6.0mg/kg,对醋酸所致小鼠扭体反应具有抑制作用,其 ED_(50)为111.7±18.1mg/kg。吲哚拉新腹腔注射30mg/kg,对四联菌苗所致家兔体温升高具有降低作用。吲哚拉新灌胃给药80mg/kg 和100mg/kg,对部分大鼠有致胃溃疡作用;同时灌胃给予白芨—甘草和角叉菜胶,剂量均为1600mg/kg,均有抗吲哚拉新致胃溃疡作用。     

两面针结晶-8镇痛作用机理的研究

作者前文报道了两面针Zanthoxylum nitidum(Roxb.)DC.根提取物N-4及从N-4中分离出的结晶-8(分子式为C_(20)H_(18)O_6,结构待定,下简称结晶-8)的解痉镇痛作用。并证明结晶-8的解痉作用是直接作用于肠平滑肌。而镇痛作用具有中枢性,并与脑内单胺类递质有关,但与脑内吗啡受体无直接关系。本文仅就结晶-8镇痛作用与中枢某些递质的作用关系加以研究。     

Characteristics of analgesia induced by noncatecholic phenylethylamine derivatives: possible involvement of endogenous opioid peptides and serotonin in phenylethylamine analog-induced analgesia

Characteristics of the analgesic action of phenylethylamine derivatives, amphetamine, phenylethylamine (PEA), hydroxyphenylethylamine (OHPEA) and hydroxyphenylalanine (OHF), were examined. Pain threshold of mice was measured by using the hot plate method. OHPEA (50 mg/kg), amphetamine (0.5-8 mg/kg) or PEA (50 mg/kg) produced an analgesic effect in the absence of MAO inhibitor, and the analgesia was reversed by naloxone (5 mg/kg) or reserpine (2 mg/kg x 2). Ten mg/kg of PEA, 250 mg/kg of OHF and 10 mg/kg of OHPEA could not produce detectable analgesia, but they revealed analgesic activity when mice were pretreated with pargyline (100 mg/kg). Analgesia induced by a combined use of PEA, OHF or OHPEA with pargyline was inhibited by naloxone or p-chlorophenylalanine (PCPA), an inhibitor of serotonin synthesis. Amphetamine-induced analgesia was also blocked by PCPA. Analgesia induced by PEA or OHPEA was blocked by methysergide (2 mg/kg). From the above findings, it was concluded that PEA, OHPEA, OHF and amphetamine possess similar characteristics in their analgesic action, and their analgesic actions involve the participation of endogenous serotonin and endogenous opioid peptides.     

Analgesic effect of caffeine and clomipramine: a possible interaction between adenosine and serotonin systems

The goals of this study were to determine whether the nonselective adenosine receptor antagonist caffeine exerts an analgesic effect and to investigate the time-dependent influence of the selective serotonin reuptake inhibitor clomipramine on the action of caffeine. Results suggest a possible interaction between serotonin and adenosine systems, which may contribute to the analgesic action of drugs. Therefore, the hot-plate and formalin tests were employed in order to measure the response to painful thermic and chemical stimuli. Results have shown that caffeine (1.67, 16.7 and 67 mg kg(-1), i.p.) exerts a direct dose-dependent analgesic action. When caffeine (1.67 and 16.7 mg kg(-1)) was combined with clomipramine (3 mg kg(-1) i.p.), an enhanced analgesic effect was obtained. However, the same combinations were ineffective in a subacute model. In this model, clomipramine was administered for 14 days and the respective dose of caffeine was added on the last day. Therefore, it can be concluded that the serotonin system interacts with the analgesic action of caffeine and that a long-term use of clomipramine probably triggers subsensitivity of adenosine receptors.     

Interactions of ketamine, naloxone and morphine in the rat

The effect of naloxone on the ketamine-induced anesthesia and analgesia, and the development of tolerance to ketamine and the cross-tolerance to morphine (measured by an analgesic effect) were investigated in the rat. Ketamine produced a dose-dependent analgesia. Naloxone, 1 mg/kg, significantly inhibited analgesia induced by ketamine, 100 mg/kg, but even in a dose of 4 mg/kg it did not affect the duration of anesthesia. A chronic administration of ketamine (100 mg/kg twice a day (b.i.d.) for 7 days) resulted in the development of tolerance to analgesic effects of ketamine. The analgesic action of morphine was attenuated in rats receiving ketamine chronically, while the analgesic effects of ketamine were significantly potentiated in morphine-dependent rats. Ketamine, 25 mg/kg, significantly attenuated the withdrawal signs evoked by naloxone in morphine-dependent rats. The results corroborate the suggestion about the participation of the central opioid neurotransmission in the mechanism of ketamine action.