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31.
目的:研究100Hz电针缓解吗啡戒断大鼠心动过速的受体机制。方法:在吗啡戒断18~24h的大鼠模型上,腹腔注射阿片受体拮抗剂纳络酮(naloxone,NX)或侧脑室注射κ阿片受体拮抗剂norbinaltorphimine(norBNI),给予100Hz电针刺激,记录吗啡戒断大鼠清醒状态下的心率和血压。结果:100Hz电针的作用可被腹腔注射NX1mg·kg-1完全翻转、被侧脑室注射NorBNI12nmol完全阻断。结论:100Hz电针抑制吗啡戒断大鼠心动过速的作用主要是通过中枢κ阿片受体介导的。 相似文献
32.
本文调查分析1所大型综合性医院1989-1994年麻醉性镇痛药使用情况,平均年消耗量为29645±s5591DDDs。年开支金额逐年增加,1994年为1990年的440%。内科用量占全院的55.3%,二氢埃托啡片1991年猛增至10万片以上,卫生部下达文件后下降。门诊麻醉镇痛药用量占4.9%,其处方量占总处方量的0.35%。主要使用单位是急诊科,占70.2%。男女患者比为2.4:1;26-45aa组占45.6%。药物利用指数0.29-0.70,使用不当者主要是二氢埃托啡,发现2人发生依赖性。43名癌痛患者很少按“三阶梯止痛疗法”给药。根据存在的问题,本文提出相应的建议。 相似文献
33.
34.
Itoh H Andoh T Watanabe I Sasaki T Kamiya Y Okumura F 《The European journal of neuroscience》2000,12(4):1253-1262
The authors have previously reported that dynorphin A (1-17), an endogenous kappa opioid agonist, inhibits the current mediated through neuronal nicotinic acetylcholine receptors (nAChRs) without the involvement of opioid receptors or G-proteins. We have further characterized this action to elucidate the mechanisms. The nicotine-induced current was studied in PC12 cells using patch-clamp techniques. In the whole-cell configuration, four kinds of dynorphins with different lengths, dynorphin A (1-17) (1-13) (2-13) and (1-8), similarly inhibited the nicotine-induced inward current at 1 microM and accelerated the current decay. The inhibition by dynorphin A (1-17) was not antagonized by the increasing concentrations of nicotine. The current-voltage relationship revealed that dynorphin's inhibition was voltage independent at the membrane potentials from -30 to -70 mV. The inhibition was not affected by pretreatment with pertussis toxin (PTX) or inclusion of staurosporine into the pipette solution. The inhibitory effect of dynorphin A (1-17) was well preserved in the outside-out patch configuration. Analysis of the nicotine-induced noise and single-channel kinetics revealed that dynorphin A(1-17) reduced open time without changing the amplitude of the unitary current. We found that the inhibitory effect on neuronal nAChRs is shared by all four dynorphins studied. The inhibition appears to be non-competitive and voltage independent. The outside-out recording together with other experiments indicated that a major part of this inhibition is not mediated through cytoplasmic messengers, but based on the direct action of dynorphins on neuronal nAChRs leading to the reduction of open time. 相似文献
35.
Valverde O Ledent C Beslot F Parmentier M Roques BP 《The European journal of neuroscience》2000,12(2):533-539
CB1 cannabinoid receptors are widely distributed in the central nervous system where they mediate most of the cannabinoid-induced responses. Here we have evaluated the interactions between the CB1 cannabinoid receptors and the endogenous opioid system by assaying a number of well-characterized opioid responses, e.g. antinociception and stress-mediated effects, on mutant mice in which the CB1 receptor gene was invalidated. The spontaneous responses to various nociceptive stimuli (thermal, mechanical and visceral pain) were not changed in mutant CB1 mice. Furthermore, the absence of the CB1 cannabinoid receptor did not modify the antinociceptive effects induced by different opioid agonists: morphine (preferential mu opioid agonist), D-Pen2-D-Pen5-enkephalin (DPDPE) and deltorphin II (selective delta opioid agonists), and U-50,488H (selective kappa opioid agonist) in the hot-plate and tail-immersion tests. In contrast, the stress-induced opioid mediated responses were modified in CB1 mutants. Indeed, these mutants did not exhibit antinociception following a forced swim in water at 34 degrees C and presented a decrease in the immobility induced by the previous exposure to electric footshock. However, the antinociception induced by a forced swim in water at 10 degrees C was preserved in CB1 mutants. These results indicate that CB1 receptors are not involved in the antinociceptive responses to exogenous opioids, but that a physiological interaction between the opioid and cannabinoid systems is necessary to allow the development of opioid-mediated responses to stress. 相似文献
36.
Monory K Bourin MC Spetea M Tömböly C Tóth G Matthes HW Kieffer BL Hanoune J Borsodi A 《The European journal of neuroscience》2000,12(2):577-584
The recently discovered endomorphin 1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin 2 (Tyr-Pro-Phe-Phe-NH2) were investigated with respect to their direct receptor-binding properties, and to their ability to activate G proteins and to inhibit adenylyl cyclase in both cellular and animal models. Both tetrapeptides activated G proteins and inhibited adenylyl cyclase activity in membrane preparations from cells stably expressing the mu opioid receptor, an effect reversed by the mu receptor antagonist CTAP (D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2), but they had no influence on cells stably expressing the delta opioid receptor. To further establish the selectivity of these peptides for the mu opioid receptor, brain preparations of mice lacking the mu opioid receptor gene were used to study their binding and signalling properties. Endomorphin 2, tritiated by a dehalotritiation method resulting in a specific radioactivity of 1.98 TBq/mmol (53.4 Ci/mmol), labelled the brain membranes of wild-type mice with a Kd value of 1.77 nM and a Bmax of 63.33 fmol/mg protein. In membranes of mice lacking the mu receptor gene, no binding was observed, and both endomorphins failed to stimulate [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding and to inhibit adenylyl cyclase. These data show that endomorphins are capable of activating G proteins and inhibiting adenylyl cyclase activity, and all these effects are mediated by the mu opioid receptors. 相似文献
37.
The c-fos gene is expressed in the central nervous system in response to various neuronal stimuli. Using in situ hybridization, we examined the effects of chronic morphine treatment and withdrawal on c-fos mRNA in the rat brain, and particularly within identified striatal neurons. Morphine dependence was induced by subcutaneous implantation of two pellets of morphine for 6 days and withdrawal was precipitated by administration of naltrexone. Placebo animals and morphine-dependent rats showed a very weak c-fos mRNA expression in all the structures studied. Our study emphasized the spatial variations in c-fos mRNA expression, and also revealed a peak expression of c-fos mRNA at 1 h after naltrexone-precipitated withdrawal in the projection areas of dopaminergic neurons, noradrenergic neurons and in several regions expressing opiate receptors. Interestingly, morphine withdrawal induces c-fos mRNA expression in the two efferent populations of the striatum (i.e. striatonigral and striatopallidal neurons) both in the caudate putamen and nucleus accumbens. Moreover, the proportions of activated neurons during morphine withdrawal are different in the caudate putamen (mostly in striatopallidal neurons) and in the shell and core parts of the nucleus accumbens (mostly in striatonigral neurons). The activation of striatopallidal neurons suggests a predominant dopaminergic regulation on c-fos gene expression in the striatum during withdrawal. On the contrary, c-fos induction in striatonigral neurons during withdrawal seems to involve a more complex regulation like opioid-dopamine interactions via the mu opioid receptor and the D1 dopamine receptor coexpressed on this neuronal population or the implication of other neurotransmitter systems. 相似文献
38.
目的设计并合成与环佐辛有类似的阿片受体亲和活性、在体内具有较长作用时间的3-四氢呋喃甲基苯并吗吩烷类似物。方法8-三氟甲磺酸酯-3-四氢呋喃甲基苯并吗吩烷经催化氨化制得目标物,对目标物进行受体亲和力测定。结果8-氨基及8-苯氨基化合物在体外与μ,δ和κ受体的亲和力均较相应的8-羟基化合物低。结论目标化合物的体外受体亲和力相对较低,但此结果尚不能完全说明其在体内的作用情况及其可否用于毒品成瘾的治疗。进一步研究正在进行。 相似文献
39.
Abstract: New analogues of deltorphin I (DT I), in which the Phe residue in position 3, and the Val residue in position 5 or 6 are replaced with respective amphiphilic α‐hydroxymethylamino acid residues (HmAA), were synthesized and tested for receptor affinity and selectivity to μ and δ opioid receptors. The analogue with (R)‐HmPhe at position 3 lost receptor selectivity, as a result of a partial decrease of affinity to δ and a significant increase of affinity to μ receptors. In contrast, an analogue with (S)‐HmPhe in the same position, was very potent and more specific to δ receptors than parent DT I. The analogue with (R)‐HmVal at position 5 expressed higher δ affinity and selectivity than parent DT I. The analogue with other possible isomer (S)‐HmVal was less selective for δ opioid receptors, as a result of decreasing affinity to δ and increasing affinity to μ receptors. The analogues with (R)‐ or (S)‐HmVal in position 6 expressed equally low receptor affinity and selectivity. The data obtained support a previously proposed model of active conformation of deltorphins. 相似文献
40.
Abstract: There is evidence to indicate that opioid compounds with mixed μ agonist/δ antagonist properties are analgesics with low propensity to produce tolerance and physical dependence. A chimeric peptide containing the potent and selective μ agonist H‐Dmt‐D‐Arg‐Phe‐Lys‐NH2 ([Dmt1]DALDA) (Dmt = 2′,6′‐dimethyltyrosine) and the potent and selective δ antagonist H‐Tyr‐TicΨ[CH2‐NH]Cha‐Phe‐OH (TICP[Ψ]) (Cha = cyclohexylalanine), connected ‘tail‐to‐tail’ via a short linker, was synthesized using a combination of solid‐phase and solution techniques. The resulting peptide, H‐Dmt→D‐Arg→Phe→Lys‐NH‐CH2‐CH2‐NH‐Phe←Cha[NH‐CH2]ΨTic←Tyr‐H, showed the expected μ agonist/δ antagonist profile in the guinea‐pig ileum and mouse vas deferens assays. Its μ and δ receptor binding affinities were in the low nanomolar range, as determined in rat brain membrane binding assays. 相似文献