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羟甲芬太尼对映异构体的镇痛活性及对阿片受体的选择性金文桥,王智贤,陈洁,陈新建,池志强(中国科学院上海药物研究所,上海200031,中国)关键词羟甲芬太尼;立体异构体;痛测定;μ阿片受体;δ阿片受体;放射配位体测定;结构活性关系目的:研究羟甲芬太尼... 相似文献
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在整体和受体水平对阿片受体拮抗剂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.与纳洛酮相比,纳曲酮强效,长效,ig有效.受体水平纳曲酮抑制[3H]羟甲芬太尼与大鼠脑阿片受体结合的强度是纳洛酮的3.6倍,与整体水平实验结果一致。 相似文献
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Human μ-opioid receptor overexpressed in baculovirus system and its pharmacological characterizations 总被引:1,自引:1,他引:0
目的:高效表达具有类似哺乳动物特性的人μ阿片受体.方法:人μ阿片受体表达在重组杆状病毒感染的Sf9昆虫细胞中,用受体结合分析和cAMP分析研究表达产物的药理学特征.结果:[3H]二丙诺啡及[3H]羟甲芬太尼(Ohm)的最大结合能力分别是9.1±0.7,652±0.23nmol/g蛋白.μ选择性激动剂对[3H]二丙诺啡或[3H]Ohm与表达受体的结合均有很强的抑制作用,而δ及κ激动剂则均无抑制作用.μ选择性激动剂有效抑制forskolin刺激的cAMP聚集,这种作用能被拮抗剂纳洛酮阻断.结论:在Sf9昆虫细胞中高效表达的人μ阿片受体保持着野生型人μ阿片受体的特征 相似文献
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以大鼠热辐射甩尾潜伏期为测痛指标,蛛网膜下腔(it)联合注射非镇痛剂量的kappa阿片受体激动剂强啡肽(dynorphin,Dyn)A-(1-13)5nmol或U50488H(trans-(±)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide)100nmol和N-methyl-D-aspartate(NMDA)受体拮抗剂DL-2-amino-5-phosphonovalericacid(APv)10nmol或kynurenicacid(KYN)50nmol有显著的协同镇痛效应,其效应与NMDA受体拮抗剂呈一定量效关系。Kappa阿片受体特异性拮抗剂nor-binaltorphi-mine(nor-BNI)15nmolit可完全翻转DynA-(1-13)5nmol和APv10nmol及U50488H100nmol和KYN50nmol的协同镇痛。说明协同作用是通过kappa受体和谷氨酸能神经元之间的相互作用实现的。 相似文献
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Modulation of intrathecal morphine-induced immunosuppression by microinjection of naloxone into periaqueductal gray 总被引:1,自引:0,他引:1
目的:观察中脑导水管周围灰质(PAG)的阿片受体和促皮质素(ACTH)在鞘内吗啡影响免疫功能时的作用和变化.方法:用铕标的靶细胞检测大鼠脾脏自然杀伤(NK)细胞活性,MTT和结晶紫蓝法分析ConA诱生的脾细胞白细胞介素2(IL2),肿瘤坏死因子TNFβ活性和血清TNFα水平,放免法测定血清促皮质素(ACTH)水平.结果:鞘内注射吗啡抑制脾NK细胞活性,ConA诱生的IL2和TNFβ活性,并伴有血清ACTH水平的上升.PAG微量注射纳洛酮部分拮抗吗啡引起的NK细胞活性的抑制,伴ACTH水平恢复.结论:PAG内的阿片受体参与鞘内注射吗啡引起的NK细胞活性的抑制,同时伴有HPA轴的激活 相似文献
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羟甲芬太尼(I)是一个新的高强度高选择性阿片μ受体激动剂。本文用cis-A-N-[1-(2-羟基-2-苯乙基)-3-甲基-4-哌啶基]-苯胺(II)或cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶基]-苯胺(III)作为前体合成了[11C]-羟甲芬太尼,以便用正电子发射断层扫描(PET)来观察μ受体。通过水解cis-A-羟甲芬太尼(I)和cis-N-[1-(苯甲酰甲基)-3-甲基-4-哌啶]-N-苯基丙酰胺(cis-IV)的4-N-丙酰基分别获得II和III。溴乙烷的格氏试剂与回旋加速器产生的[11C]-二氧化碳反应后继而直接加入邻苯二甲酸二酰氯和2,6-二叔丁基吡啶生成同位素标记中间体[11C]-丙酰氯。[11C]-丙酰氯与OH-前体(II)反应后再经HPLC分离纯化直接得[11C]-羟甲芬太尼;[11C]-丙酰氯与酮-前体(III)反应后,再用硼氢化钠甲醇溶液处理,然后进行HPLC分离纯化得[11C]-羟甲芬太尼。两种方法均可获得ll.1~14.8GBq/μmol的特异性放射化学纯[11C]-羟甲芬太尼。总共耗时为40~50min(EOB)。 相似文献
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目的:观察降钙素对大鼠不同脑区痛阈的影响.方法:向大鼠不同脑区注射降钙素(calcitonin,Cal),以辐射热甩尾阈值为指标测定痛阈变化.结果:Cal侧脑室(VLC)注射引起痛阈明显升高;同时发现向中脑导水管周围灰质(periaquaductalgrey,PAG)注射Cal,痛阈升高幅度更大,表明PAG在Cal的中枢镇痛效应中起重要作用.而向缰核(habenula,Hab)注射Cal,痛阈降低.Cal对痛阈的影响与脑内Ca2+有关. 相似文献
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Antagonistic effect of orphanin FQ on opioid analgesia in rat 总被引:5,自引:1,他引:4
目的:研究孤啡肽(OFQ)对痛与阿片镇痛的影响.方法:脑室(icv)与鞘内(ith)给药,以大鼠甩尾模型测痛.结果:小剂量OFQ(01μg)icv及ith给药对痛反应均无影响;较大剂量OFQ(05-10μg)可使痛反应增强.OFQ1-10(OFQ的一个片段)icv对痛反应无影响.μ受体激动剂芬太尼(1μg)、δ激动剂DSLET(5μg)icv或ith给药,以及κ激动剂U50488H(1μg)ith给药,可使痛阈明显增加.01μg或1μgOFQ与上述药物合用后,痛阈增加明显减少(除鞘内与DSLET合用外).结论:OFQ可增强大鼠的痛反应,在脑内对抗由μ和δ受体介导的阿片镇痛,在脊髓对抗由κ和μ但不是由δ受体介导的镇痛. 相似文献
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羟甲芬太尼是一种强效镇痛药,本实验采用3种动物、3种药物精神依赖性评价方法对其精神依赖性潜力进行系统评价,结果表明羟甲芬太尼存在着一定的精神依赖性潜力,但等效剂量的羟甲芬太尼的精神依赖性潜力低于吗啡,同时对其依赖性机理进行初步探讨推测其药物强化效应可能是通过阿片μ-受体起作用的。 相似文献
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痛稳素碳末端八肽翻转孤啡肽对抗吗啡镇痛的作用 总被引:1,自引:0,他引:1
目的 观察痛稳素碳末端八肽在小鼠脑内对孤啡肽对抗吗啡的镇痛作用的影响。方法 固相多肽合成法合成了痛稳素碳末端八肽 ,用辐射热甩尾法测定痛阈 ,观察 (1)小鼠脑室注射 (icv)孤啡肽对吗啡镇痛作用的影响 ;(2 )小鼠脑室注射 (icv)痛稳素碳末端八肽对小鼠基础痛阈的影响 ;(3)小鼠脑室联合注射 (icv)痛稳素碳末端八肽和孤啡肽对吗啡镇痛作用的影响。结果 孤啡肽可对抗吗啡的镇痛作用 ;痛稳素碳末端八肽本身不影响小鼠的基础痛阈 ,但可逆转孤啡肽对抗吗啡的镇痛作用。结论 痛稳素碳末端八肽在脊髓以上水平可以逆转孤啡肽对抗吗啡的镇痛作用 相似文献
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The antinociceptive effects of O-methylflavinantine (OMF), a morphinandienone alkaloid, were investigated in the mouse hot plate and abdominal constriction tests (nociceptive agents: 5-Hydroxytryptamine, acetylcholine, bradykinin, prostaglandin, E (1) (PGE (1), formic acid and phenylquinone). The potency of OMF in the hot plate test was approximately 10 times less than that of morphine and the effect was naloxone reversible. In the abdominal constriction test, morphine was 78-650 times more potent than OMF, depending on the nociceptive agent used, but a higher dose of naloxone was necessary to reverse the response to formic acid. Pretreatment of mice with reserpine (1 mg/kg, s.c., 24 h) reduced and alpha-methyl-p-tyrosine (200 mg/kg, i.p., 3 h) potentiated the antinociceptive effects of both morphine and OMF in the hot plate test. The results are considered to indicate that OMF possesses centrally mediated antinociceptive activity which is similar to that of morphine. 相似文献
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孤啡肽与八肽胆囊收缩素在大鼠脑内拮抗吗啡镇痛的协同作用 总被引:6,自引:4,他引:2
目的观察孤啡肽(OFQ)和八肽胆囊收缩素(CCK 8)在大鼠脑内拮抗吗啡镇痛是否具有协同作用。方法应用等高线法设计实验,用辐射热甩尾法测定痛阈。皮下注射吗啡(5mg·kg-1)20min之后,选择有明显镇痛效应的大鼠,侧脑室(icv)分别注射不同剂量的OFQ和CCK 8以及由两者不同比例(5∶1,25∶1)不同剂量组成的混合物,观察对吗啡镇痛效应的影响。结果联合应用OFQ和CCK 8所产生的抗吗啡镇痛作用明显大于单独使用OFQ或CCK 8。结论OFQ和CCK 8在一定比例、一定剂量组合范围内,对抗吗啡镇痛具有协同效应。 相似文献
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用大鼠甩尾法和放射配基结合实验,探讨了可乐定镇痛与中枢Ca2+的关系。CaCl2(1μmol/rat,icv)和EGTA(0.2μmol/rat,icv)分别拮抗和增强可乐定(1mg/kg,sc)的镇痛。戊脉安(0.1μmol/rat,icy)对可乐定(1 mg/kg,sc)镇痛无明显影响,但可部分翻转CaCl2对可乐定镇痛的拮抗。CaCl2(1×10-3mol)对[3H]-可乐定结合无明显抑制。结果表明可乐定镇痛与脑室周围组织中Ca2+浓度变化密切相关,Ca2+至少部分需经对戊脉安敏感的钙通道进入细胞内方可拮抗可乐定镇痛。推沦:可乐定镇痛与神经元内Ca2+有关。 相似文献
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Intrathecal N-methyl-D-aspartate (NMDA) induces paradoxical analgesia in the tail-flick test in rats
Alvarez-Vega M Baamonde A Gutiérrez M Hidalgo A Menéndez L 《Pharmacology, biochemistry, and behavior》2000,65(4):621-625
The intrathecal (IT) administration of NMDA in rodents has usually been reported to produce hyperalgesic reactions, although some articles describe that spinal NMDA can lead to analgesia. We show here that the nociceptive behavior (biting, scratching, licking; BSL) observed after NMDA injection (1-8 microg/rat; IT) is followed by a long period of increased tail-flick latencies, not longer detected 24 h after NMDA administration. The NMDA-receptor antagonist CPP (10-100 ng/rat; IT) blocked the BSL behavior induced by NMDA. In the tail-flick test, this antagonist induced analgesia by itself, and was able, at 30 ng/rat, to prevent the NMDA-mediated analgesia. The implication of opiate mechanisms was discarded since naloxone (3 and 10 mg/kg; IP) did not antagonize NMDA-induced analgesia. Finally, the involvement of the intracellular calcium binding protein calmodulin was assessed. The calmodulin inhibitor, calmidazolium (30-300 microg/rat; IT) only blocked the excitatory effect (BSL) without modifying the tail-flick analgesia produced by NMDA (4 microg). These results show that a single intrathecal administration of NMDA sequentially induces both nociceptive and antinociceptive, nonopiate responses in rats. 相似文献
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Imipramine and amitriptyline, nonselective monoamine reuptake inhibitors, citalopram, selective serotonin reuptake inhibitor, and maprotiline, selective noradrenaline reuptake inhibitor, were tested after intracerebroventricular (icv) and intrathecal (it) administration in the rat writhing test to establish the role of the spinal and/or supraspinal structures in their effects. All drugs evoked dose-dependent analgesia after icv but not after it microinjections. The changes in the nociceptive behavior of rats pre-treated with antidepressants were not due to the non-specific influences of the drugs on the animals' gross behavior, as revealed by the open field test. The obtained results suggest that an antidepressant-induced analgesia mainly depends on the supraspinal effect with minor, if any, contribution from the spinal mechanisms. 相似文献
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I Padovano G Matera R De Pasquale G Costa A P Caputi 《Polish journal of pharmacology and pharmacy》1985,37(4):495-501
Intracerebroventricular (icv) injection of pentagastrin showed a powerful, dose dependent antidipsogenic effect in the rat. Drinking behavior stimulated by 48 h water deprivation was inhibited by 2000 ng of pentagastrin which also blocked, at lower doses, water intake induced by icv injection of angiotensin II (100 ng) and carbachol (150 ng). Pentagastrin was less effective on food intake stimulated by 24 h starvation. The antidipsogenic effect was not a consequence of behavioral alteration. It is suggested that gastrin-like peptides in the brain may play a role in the regulation drinking, acting as thirst inhibitors. 相似文献
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