云南狗牙花总碱的镇痛作用

目的：研究云南狗牙花总碱（total Ervamia yunnansis alkaloid，TEYA）对小鼠的镇痛作用。方法：采用小鼠热板法，观察TEYA的镇痛作用及对吗啡的镇痛作用的影响：结果：与同期对照组相比，TEYA的3个剂量组均可显著提高小鼠的痛阈值，镇痛效果随剂量的增加呈剂量依赖关系；同时给予TEYA（10、20mg／kg）和吗啡4mg／kg，有协同镇痛的作用；纳洛酮4mg／kg可以部分拮抗TEYA的镇痛作用。结论：TEYA有明显的镇痛作用，其作用可能部分通过阿片受体来实现。     

狗牙花总生物碱的身体依赖性实验研究

目的评价狗牙花总生物碱的身体依赖性潜力。方法采用小鼠催促戒断和大鼠自然戒断模型对狗牙花总生物碱进行身体依赖性实验。结果在小鼠催促实验中,给予狗牙花总生物碱低剂量(140mg/kg)、高剂量(430mg/kg),连续注射7d,而后经纳洛酮激发,实验小鼠未出现明显的戒断症状、跳跃次数增加和体重下降现象。在大鼠自然戒断实验中,给予狗牙花总生物碱低剂量(210mg/kg)、高剂量(775mg/kg),连续注射30d,停药后未见大鼠出现戒断反应和体重下降现象。结论狗牙花总生物碱无身体依赖性。     

海南狗牙花总生物碱对兔实验性动脉粥样硬化的影响

本文报告海南狗牙花总生物碱(以下称总碱)对实验性动脉粥样硬化兔血清、主动脉和肝脏脂质含量,以及对动脉粥样硬化的影响。总碱能明显降低血清胆固醇(S-Ch)和甘油三酯(S-TG)含量,增加血清高密度脂蛋白胆固醇(HDL-Ch)含量和游离胆固醇(FC)与胆固醇酯(CE)的比值;能使主动脉壁胆固醇含量降低,FC与CE的比值增加,亦能明显减轻动脉粥样硬化的发展。总碱对肝脏脂质含量无明显影响。     

紫花高乌头总碱对吗啡依赖大鼠CYP2E1代谢活力的影响

目的:观察紫花高乌头总碱对吗啡依赖大鼠CYP2E1代谢活力的影响。方法:采用剂量递增法建立吗啡依赖大鼠模型,注射纳洛酮催促产生戒断症状,高效液相色谱法(HPLC)测定经CYP2E1代谢的探针药物氯唑沙宗血药浓度经时变化。结果:吗啡依赖可致大鼠CYP2E1对探针药物氯唑沙宗的代谢活性增强,催促戒断可致体重减轻,CYP2E1对探针药物氯唑沙宗的代谢活性进一步增强。紫花高乌头总碱可降低大鼠的戒断反应症状分值,控制大鼠的体重下降,下调吗啡依赖所致的CYP2E1的代谢活性增强。结论:紫花高乌头总碱可抑制吗啡依赖大鼠的戒断症状,使吗啡依赖及其催促戒断后增高的CYP2E1代谢活力下调。     

钩藤总碱、钩藤碱和异构藤碱的药理作用

The pharmacvological actions of Uncaria alkaloids,rhyncopyline and isorhnchophyline extracted from Uncaria rhynchophylla Miq Jacks were reviewed.The alkaloids mainly act on cardiovascular system and central nervous system including the hypotension,brachycardia,antiarrhythmia,and protection of cerebral ischemia and sedation. The active mechanisms were related to blocking of calcium channel,opening of potassium channel,and regulating of nerve transmitters transport and metabolism,etc.     

青藤碱对吗啡依赖小鼠位置偏爱效应的影响

目的 :利用条件性位置偏爱实验研究中药成分青藤碱对小鼠吗啡奖赏效应的影响。方法 :实验采用有倾向性程序。吗啡 (9mg· kg-1,sc,每日 1次 ,5 d)引起小鼠显著的位置偏爱效应。在训练阶段每天 sc吗啡前3 0 min预先给予青藤碱 (1 0 ,3 0和 60 mg· kg-1,ip)可剂量依赖性地抑制吗啡引起的小鼠位置偏爱效应。结果 :提示预先给予青藤碱能消除吗啡产生的条件性位置偏爱。     

苦参总碱片抗心血管系统疾病的药理作用

苦参总碱片是由豆科植物苦参的干燥根经渗漉法提取，精制而得的苦参总碱浸膏，再加入适宜的辅料制剂而成。苦参总碱中含多种生物碱，主要为苦参碱和氧化苦参碱；另外还含有羟基苦参碱、去氧苦参碱、安那吉碱、N-甲基金雀花碱等及多种黄酮类。苦参总碱具有抗心率失常，增加冠脉流量，保护心肌缺血、增加心肌收缩力、降血脂、抗肝炎、抗肿瘤、防止白细胞减少、抗辐射、抗过敏、镇痛平喘、祛痰等作用。本文就苦参总碱片的抗心血管疾病方面的作用予以综述。     

灯盏花素防治脑卒中的药理作用研究和临床验证

神经细胞内钙超载、细胞外兴奋性氨基酸(ＥＡＡ)堆积、氧自由基生成增加、蛋白激酶Ｃ(ＰＫＣ)的过度激活或位移激活是国内外大多数学者公认的缺血导致脑损伤或神经细胞凋亡的4大因素,因此,能防止血栓形成、溶解血栓、改善血液流变学、抑制血小板聚集、加快脑血流速度、增加脑血流量、改善脑微循环、抑制ＰＫＣ过度激活或位移激活、抑制ＥＡＡ氨基酸胞外堆积和细胞内钙超载、防止氧自由基生成增加的药物都能防治缺血性脑神经功能受损和神经细胞凋亡。灯盏花素是目前具上述功能较全面的药物,因而成为防治缺血性和出血性脑血管病后遗症的首选药…     

紫花高乌头总碱对吗啡依赖大鼠氯唑沙宗药动学的影响

目的:观察紫花高乌头总碱对吗啡依赖大鼠氯唑沙宗药动学的影响。方法:采用剂量递增法复制吗啡依赖大鼠模型,注射纳洛酮催促产生戒断症状,高效液相色谱法测定经CYP2E1代谢的探针药物氯唑沙宗血药浓度经时变化。结果:吗啡依赖可致大鼠CYP2E1对探针药物氯唑沙宗的代谢活性增强,AUC减少,Cmax减少。催促戒断可致体质量减轻,CYP2E1对探针药物氯唑沙宗的代谢活性进一步增强。紫花高乌头总碱可降低大鼠的戒断反应症状分值,控制大鼠的体质量下降,下调吗啡依赖所致的CYP2E1的代谢活性增强。结论:紫花高乌头总碱可抑制吗啡依赖大鼠的戒断症状,使吗啡依赖及其催促戒断后增高的CYP2E1代谢活力下调。     

青藤碱对小鼠吗啡的精神依赖以及cAMP水平的影响

目的　观察中药单体成分青藤碱 (sinomenine ,Sin)对吗啡诱导的小鼠精神依赖及其中枢cAMP水平的变化的影响。方法　采用有倾向性程序引起小鼠显著的位置偏爱效应 ,利用条件性位置偏爱实验观察ipSin 10、30、6 0mg·kg-1对小鼠吗啡奖赏效应的影响 ,用放射免疫法测定小鼠脑中cAMP含量。结果　Sin可剂量依赖性地缩短小鼠在吗啡伴药箱的时间 ,对吗啡慢性作用引起的小鼠脑内cAMP含量增加具有抑制作用。结论　Sin能减弱小鼠对吗啡的精神依赖 ,降低中枢cAMP水平 ,且其本身未显示精神依赖性反应。     

The effect of morphine on vagal inhibition of the heart

The action of morphine (0.1 to 100 mg./kg.) on the cardiac slowing produced by stimulation of the right vagus nerve varied in the four species investigated. In the guinea-pig, morphine had no inhibitory effect and in the cat the effect was small, but in the rat and the rabbit stimulation of the vagus slowed the heart much less after administration of morphine than before. Further, in the last two species morphine delayed the onset of cardiac slowing. Nalorphine, which given alone had a slight morphine-like action, partly reversed the effect of morphine.     

Protective effect of bupropion on morphine tolerance and dependence in mice

Possible reversal of morphine-induced tolerance and dependence by bupropion was studied in mice. A 10-day repeated injection regimen was followed to induce morphine tolerance and dependence. Bupropion (2 and 5 mg/kg) per se, when chronically administered for 9 days, failed to produce any significant change in tail-flick latency compared with the control mice. Chronic administration of bupropion (2 or 5 mg/kg) during the induction phase (days 1-9) delayed the development of tolerance to the antinociceptive action of morphine and also reversed naloxone- (2 mg/kg) precipitated withdrawal jumps. On the other hand, acute administration of bupropion (2 or 5 mg/kg) on day 10, i.e., during the expression phase of morphine dependence, reduced the incidence of naloxone-precipitated withdrawal jumps without affecting tolerance to the analgesic effect. In conclusion, results of the present study suggest the potential use of bupropion in tolerance and dependence.     

Drug-seeking behavior in the dog: lack of effect of prior passive dependence on morphine

Twelve dogs were made dependent on morphine (20 mg/kg per 24 hours) by intravenous passive administration of the drug. Six were gradually withdrawn and six were withdrawn abruptly. Subsequent tests for self-administration of morphine began within 8 to 18 weeks after morphine was last administered passively. Morphine was available for self-administration at several unit dose levels for 8 weeks. In comparison with control dogs administered with saline, there was no evidence that prior dependence on morphine influences subsequent self-administration of morphine, or that morphine is a primary reinforcer for dogs. Possible implications of these and related observations are discussed.     

The effect of aspartic acid on the intensity of physical dependence in morphine dependent mice

The mice (Balb/C strain) given 2% aspartic acid in 5% saccharose solution or only saccharose solution (p. os) starting 12 hr before the sc morphine pellet implantation until the removal of pellet were rendered physically morphine dependent. During the development of morphine dependence and after the removal of pellets (on 3-d day) spontaneous motor activity and analgesic threshold were measured as reliable abrupt withdrawal signs. Aspartic acid prevented to some extent the appearance of symptoms of physical morphine dependence.     

Lack of effect of dexoxadrol in self-maintained morphine dependence in rats

Summary Dexoxadrol, dextromethorphan and meperidine were given by continuous intravenous infusion to selfmaintained morphine dependent rats. Dexoxadrol and dextromethorphan did not significantly decrease the rate of morphine self-administration. Meperidine produced a dose related decrease in the rate of morphine injections. The failure of dexoxadrol to reduce morphine intake is evidence that it will probably not produce opioid-like addiction liability in man.     

Effects of α-methyl-p-tyrosine on morphine dependence

The effects of alpha-methyl-p-tyrosine (aMpT) on the initial liability to consume oral morphine solution and on withdrawal following cessation of passive morphine administration were assessed. aMpT depressed consumption of oral morphine solution if aMpT was administered throughout a nine day period of morphine intake; when aMpT administration was stopped a day prior to presentation of morphine solution, subsequent intakte of morphine was enhanced. Following cessation of passive morphine administration, aMpT was found to ameliorate withdrawal-induced weight loss; this effect occurred to a similar extent regardless of whether aMpT was administered only during the first withdrawal day, only on days of morphine administration or during both periods of morphine administration and withdrawal. These results implicate an important role of catecholamines in addiction and dependence to morphine.This research was supported by grants DA00535 from NIMH, U-2177 from the Health Research Council of the City of N.Y. and by NIMH Research Scientist Development Award (Type 2) DA70082 to S. D. Glick. The authors thank Richard Marsanico for indispensable technical assistance.     

Acute morphine dependence in the hamster

Two experiments investigated naloxone-precipitated withdrawal following a brief course of morphine administration in hamsters. In Experiment 1, observable withdrawal symptoms (e.g., wet-dog shakes) were elicited by two doses of naloxone (0.4 and 1.0 mg/kg) following four and eight daily injections of morphine (15 mg/kg), a regimen that replicated previous studies in our laboratory using a locomotor activity paradigm. At the lower dose of naloxone, the frequency of withdrawal signs was greater after eight than after four morphine injections. In Experiment 2, observable withdrawal symptoms were elicited by the same two doses of naloxone, 70 min after a single morphine injection. These results suggest that acute dependence in the hamster, as in other species, beings to develop with the first morphine exposure.     

Antidiuretic effect of morphine in the rat: tolerance and physical dependence.

1 Injection of rats with morphine or methadone, before they received a water load equivalent to 5% of their body weight, produced a dose-dependent antidiuretic effect. Following the antidiuresis, urine was eliminated with kinetics similar to control untreated rats. 2 The antidiuretic effect of morphine or methadone was blocked by naloxone administered before the opiate, or reversed when given after the opiate. 3 Rats implanted with morphine pellets developed a marked degree of tolerance to the antidiuretic effect of morphine. Tolerance was also obtained on injection of three daily doses of morphine or methadone over two days. 4 Withdrawal symptoms were precipitated by naloxone in rats implanted with pellets of morphine; under these conditions the animals showed a marked reduction in urine production as compared to naive rats.     

钙调素与吗啡依赖

药物依赖是一种中枢神经系统长时程生物学效应 (ｌｏｎｇ-ｔｅｒｍａｄａｐｔａｔｉｏｎ)。药物依赖的形成可能需要新的肽或蛋白质的合成 ,涉及到受体后的信号转导 ,基因的转录 ,翻译和调控 ,效应子 (ｅｆｆｅｃｔｏｒ)的表达及其生物学效应的产生。在药物依赖的形成过程中 ,长时程信号转导分子的适应性变化 (ｌｏｎｇ-ｔｅｒｍｓｉｇｎａｌｉｎｇ ｍｏｌｅｃｕｌａｒａｄａｐｔａｔｉｏｎ)至少表现出３个方面的生物学效应 :（１）躯体调控系统 ( ｐｈｙｓｉｃａｌｃｏｎｔｒｏｌｓｙｓｔｅｍ) :包括自主神经系统和其它躯体功能的改变 ;（２…