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991.
(1) Affinity and intrinsic activity values of 75 compounds for a histaminergic and a cholinergic system are presented. The quantitative correlations between the affinity values of 35 compounds and some physicochemical constants (Van der Waals volume, lipophilicity, number of hydrogen atoms on the protonated amine) are discussed. (2) Absence of systematic differences between pD2 and pA2 of partial agonists supports the assumption that these values are equivalent expressions of the same affinity. (3) The "mimetic moiety" in a number of the antihistaminic test compounds hardly contributes to their affinity. The affinity mainly depends on an interaction tendency with additional receptor areas. (4) The correlation between pA2 and pD2' of the whole series of compounds in the histaminergic system is artificial. The method only allows determination of both values if their ratio lies between certain limits. (5) The correlation between pA2 and pD2' for 16 closely related compounds in the guinea pig ileum and for nearly all compounds in the rat intestine has to be explained by an influence of the structural differences on drug transference and/or the less specific binding forces. (6) The metactoid receptors in the two systems are different structures. (7) Possible molecular modifications to maximize the separation of antihistaminic form cholinergic affinity are suggested. 相似文献
992.
A. Dittrich P. Bickel J. Schöpf D. Zimmer 《European archives of psychiatry and clinical neuroscience》1976,223(1):77-87
Zusammenfassung Die Untersuchung vergleicht unter Verwendung zweier Placebo-Kontrollgruppen veränderte Bewußtseinszustände, die unter den Halluzinogenen (–)9-trans-Tetrahydrocannabinol (9-THC) und N,N-Dimethyltryptamin (DMT) auftreten. 24 Probanden erhielten 250g 9-THC p.o. pro kg Körpergewicht, und 26 Probänden wurde 250g DMT pro Körpergewicht i.m. appliziert. Die Placebogruppe bestand aus insgesamt 24 Probanden. Die Effekte wurden retrospektiv mit einem Fragebogen erfaßt, dessen Items nach inhaltlichen und testtheoretischen Gesichtspunkten zu den folgenden 8 Skalen zusammengefaßt wurden: Optische Sinnestäuschungen, akustische Sinnestäuschungen, Konzentrations- und Gedächtnisstörungen, Derealisationserscheinungen, Depersonalisationserscheinungen, Leiberlebensveränderungen, euphorisches Zustandsbild und dysphorisches Zustandsbild.In allen acht Syndromen unterschieden sich die beiden Halluzinogene signifikant von Placebo. Zwischen den Halluzinogenen konnte jedoch keine signifikante Differenz nachgewiesen werden. In der Skala optische Sinnestäuschungen zeigte sich als Tendenz, daß DMT hier eine stärkere Wirkung als 9-THC entfaltet.Methodische Probleme des Vergleichs verschiedener Halluzinogene werden diskutiert. 相似文献
993.
Previous results suggest that norepinephrine decreases growth hormone (GH) release in goldfish by means of alpha-2 adrenoceptor activation. The intracellular mechanisms by which norepinephrine inhibits GH release were examined in the present study using dispersed goldfish pituitary cells. In 2-h static incubation experiments, norepinephrine and the alpha-2 agonist clonidine decreased basal GH release and the GH responses to stimulation by the dopamine D1 agonist SKF38393 and two native gonadotropin-releasing hormones (GnRH). Norepinephrine also reduced GH responses to the adenylate cyclase activator forskolin, two protein kinase C (PKC) activators (phorbol ester and synthetic diacylglycerol), and two Ca2+ ionophores (ionomycin and A23187). Similarly, norepinephrine applied as a 1-h pulse in cell column perifusion experiments reduced basal GH release and abolished the GH response to a 5-min pulse of arachidonic acid. In goldfish, D1-stimulated GH release is mediated by AC-, arachidonic acid-and Ca2+-dependent pathways, whereas GnRH action is coupled to PKC-and Ca2+-dependent mechanisms. These results suggest that norepinephrine activation of alpha-2 receptors inhibits ligand-induced GH secretion by actions subsequent to activation of these second messenger cascades. To further characterize norepinephrine mechanisms of action on unstimulated hormone release, the ability of norepinephrine and an alpha-2 agonist to affect activation of two second messenger cascades under basal conditions was also investigated. Static incubation with clonidine reduced cAMP production in a time-and dose-dependent manner, suggesting that norepinephrine inhibitory action can also be expressed at the level of cAMP production. Resting intracellular free calcium levels in single, identified goldfish somatotropes was unaffected by norepinephrine. However, the inhibitory effects of norepinephrine on basal GH secretion was not observed in the presence of a voltage-sensitive Ca2+ channel agonist. Whether these channels are targets for norepinephrine action on unstimulated GH release requires further investigation. 相似文献
994.
Williams B Bence M Everest H Forrest-Owen W Lightman SL McArdle CA 《Journal of neuroendocrinology》2000,12(2):159-166
gamma-amino butyric acid (GABA) is the major inhibitory neurotransmitter in the CNS, mediating fast inhibitory synaptic transmission, by activating GABAA receptors. However, these GABA-gated Cl- channels can also be excitatory, causing depolarization, and increasing Ca2+ entry via voltage-operated Ca2+ channels (VOCCs). Evidence exists for excitatory ionotropic GABA receptors in anterior pituitary cells, including gonadotropes, but these have not been directly characterized and their pharmacology remains controversial. Here we have measured the cytosolic Ca2+ concentration ([Ca2+]i) in alphaT3-1 gonadotropes, to test for expression of excitatory GABA receptors. The GABAA agonists, GABA and muscimol, both caused rapid, robust and dose-dependent increases in [Ca2+]i (EC50 values 2.7 and 1 microM), whereas the GABAB agonist, baclofen, did not. The GABAA antagonist, bicuculline, inhibited muscimol's effect, whereas the GABAB antagonist, phaclofen, did not. The neuroactive steroid 5alpha-pregnan-3alpha-ol-11,20-dione (an allosteric activator of GABAA receptors) increased [Ca2+]i, and this effect, like that of muscimol, was inhibited by picrotoxin. The muscimol effect on [Ca2+]i was blocked by the VOCC antagonist, nifedipine, or by Ca2+-free medium. When cells were pretreated with muscimol this increased the spike phase of the [Ca2+]i response to subsequent stimulation with gonadotropin-releasing hormone (GnRH). Similar amplification was seen in muscimol-pretreated cells stimulated with GnRH in Ca2+-free medium, but not when cells were pretreated with muscimol in Ca2+-free medium. The amplification was not, however, GnRH receptor-specific, because the spike response to ionomycin was also increased by muscimol pretreatment. These data provide the first direct evidence for expression of excitatory GABAA receptors, and the first demonstration of acute steroid effects, on GnRH-responsive pituitary cells. They also reveal a novel mechanism by which GABAA activation modulates GnRH action, raising the possibility that this may also influence gonadotrophin secretion from non-immortalized gonadotropes. 相似文献
995.
目的:探讨多药耐药集团(MDR1)在小细胞肺癌化疗中的作用和地位,方法:采用逆转录-多聚酶链式反应技术(RT/PCR)和免疫细胞化学染色法,检测了32例(初治原发癌21例和复治转移癌11例)小细胞肺癌患者血液中的MDR1mRNA水平和多药耐药蛋白(P-170)的表达,并对两种方法进行了比较。结果:初治的原发癌MDR1基因阳性表达率为14.29%,P-170蛋白阳性表达为14.27%,复治转移癌的MDR1基因阳性表达率为72.73%,P-170蛋白阳性表达为63.64%(P<0.01),有显著性差异。MDR1的基因和蛋白两种而检测方法具有一定的一致性,以RT/PTR方法具有更强的敏感性,结论:复治转移癌组比初治组具有更普遍的抗药性,且主要是获得性抗药,MDR1基因表达可作为临床合理地制定化疗方案,预测化疗效果的重要参考指标。 相似文献
996.
益气活血中药对放射性骨损伤防护作用的实验研究 总被引:2,自引:0,他引:2
目的 :探讨益气活血中药防治放射性骨损伤的作用。方法 :60Coγ射线一次 3 0Gy照射兔后腿造模 ,实验组用中药 6个月 ,对照组不做治疗。不同时相观察照射部位骨细胞、血管变化、血管铸型、血流情况。结果 :骨细胞变性坏死在呈持续发展 ,尤其第 6周时尤为明显 ,对照组为 2 7% ,实验组为 8% ,差异明显 ,血管铸型 1 3周血管网逐增加 ,呈囊性扩张融合成片 ,以后渐减少 ,2 4周时实验组血管数目明显多于对照组。血流两组 3周时为著 ,6周后呈持续下降 ,但对照组明显 (P <0 .0 1 )。讨论 :益气活血中药能减轻射线对骨细胞及其它组织的直接杀伤 ,减轻对骨血管损伤 ,改善骨微循环及血流。 相似文献
997.
998.
999.
目的:观察纯中药制剂银康颗粒剂治疗银屑病的,临床疗效及治疗前后患者血粘度的变化。方法:将382例患者随机分为2组,治疗组252例应用银康颗粒剂治疗,对照组130例应用复方青黛胶囊治疗;对治疗组部分病例(212例)治疗前后血粘度指标进行观察。结果:治疗组治愈148例,好转82例,未愈22例,总有效率为91.12%;对照组治愈51例,好转46例,未愈33例,总有效率为74.62%,2组总有效率比较,差异有非常显著性意义(P<0.01)。治疗组患者治疗前后全血粘度差异无显著性意义(P>0.05),血浆粘度差异有显著性意义(P<0.05)。结论:风邪外袭、血虚生风、气滞血瘀是致病的主要原因。治疗应以清热祛风与养血活血并举。 相似文献
1000.
通腑泄热豁痰法治疗急性脑出血42例疗效观察 总被引:5,自引:0,他引:5
目的:观察通腑泄热豁痰法治疗急性脑出血的临床疗效。方法:将80例患者随机分为2组。治疗组42例根据病情对症采用西医常规处理,并口服或鼻饲通腑泄热豁痰方药;对照组38例以常规西药治疗。2组均以4周为1疗程,观察2组疗效及意识状态、运动功能的变化。结果:治疗组显效32例,有效3例,无效2例,死亡5例,总有效率83.3%;对照组显效19例,有效4例,无效6例,死亡9例,总有效率60.5%。2组总有效率比较,差异有显著性意义(P<0.05)。治疗组治疗后意识状态及运动功能评分均显著提高(P<0.001)。结论:通腑泄热豁痰方药对急性脑出血效果显著优于常规西药治疗。 相似文献