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排序方式: 共有485条查询结果,搜索用时 15 毫秒
61.
F I Carroll Y G Gao M A Rahman P Abraham K Parham A H Lewin J W Boja M J Kuhar 《Journal of medicinal chemistry》1991,34(9):2719-2725
A series of 3 beta-(p-substituted phenyl)tropane-2 beta-carboxylic acid methyl esters (2) were synthesized and found to possess high affinity for the cocaine binding site in rat striatum. The p-chloro (2c) and p-iodo (2n) compounds, which were the most potent analogues prepared, were found to be 85 and 78 times more potent than (-)-cocaine. The p-bromo (2m) and p-methyl (2d) were also 56 and 60 times more potent than cocaine. QSAR and CoMFA studies were conducted to correlate binding affinity of the cocaine analogues with their structural features. Whereas the QSAR study gave relatively low correlations, the CoMFA study gave a correlation with high predictive value. 相似文献
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Frederick Batzold Robert Dehaven Michael J. Kuhar Nigel Birdsall 《Biochemical pharmacology》1980,29(18):2413-2416
Sodium-dependent, high affinity choline uptake in brain synaptosomes was inhibited by various choline analogues. When substituents were placed on the quaternary nitrogen, the compounds became weaker inhibitors as the bulk of the substituents increased. None of the compounds with changes in the hydroxyl group part, except for a bis-quaternary compound, were potent inhibitors. Increasing the oxygen-nitrogen distance resulted in a weaker inhibition. Data from crystallographic studies [M. E. Senko and M. Templeton, Acta crystallogr. 13, 281 (1960); and F. G. Canepa, Nature, Lond.207, 1152 (1965)] and inspection of Dreiding molecular models suggest an optimal oxygen-nitrogen distance of about 3.3 Å. These results support earlier suggestions that a hydroxyl group and a quaternary nitrogen are necessary for interaction with the carrier. 相似文献
65.
The postnatal development of the distribution of opiate binding sites in the rat forebrain was studied by light microscopic autoradiography. [3H] dihydromorphine ([3H]DHM) was used to label receptors in the forebrain of neonates days 2, 6, 8, 12, 16 and 21 postpartum. The hippocampus of the 2-day-old rat was diffusely labeled by [3H]DHM. By day 8, autoradiographic grains had a different distribution and were now clustered around the pyramidal cells. By day 16, the adult distribution of opiate binding sites was established. These changes correlate with the development of this structure and suggests that these binding sites may be localized to inhibitory interneurons of the pyramidal cell layer. The appearance of specific binding sites in the stratum moleculare of the dentate gyrus at day 8 further correlates with the development of the granule cells and their dendritic processes. In the olfactory bulb, high levels of specific binding were seen in the external plexiform layer at day 2. This pattern gradually changed, so that in the adult, the binding sites were more enriched in the glomeruli and granule cell layer. These changes in the olfactory bulb may be related to the maturation of the tufted cells and granule cells. Other regions of the brain were also examined. Thus, the analysis of receptor binding in development can aid in the localization of receptors to specific neuronal elements. 相似文献
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Quantitative receptor autoradiography using [3H]ultrofilm: application to multiple benzodiazepine receptors 总被引:21,自引:0,他引:21
J R Unnerstall D L Niehoff M J Kuhar J M Palacios 《Journal of neuroscience methods》1982,6(1-2):59-73
Radiohistochemical methods utilized to label drug and neurotransmitter receptors in vitro at the light microscopic level are quantitative. In this report, the response of tritium-sensitive sheet film ([3H]Ultrofilm) was characterized under conditions used for the light microscopic localization of neurotransmitter receptors by in vitro autoradiographic techniques. Radioactive standards containing varying concentrations of tritium were prepared from brain tissue and exposed to [3H]Ultrofilm for varying lengths of time, and the response of the film was measured by microdensitometry. A 1n optical density versus 1n radioactivity plot provided a useful linear relationship. Relationships established between radioactivity concentrations, exposure times and optical density were utilized to establish appropriate exposure conditions for several [3H]ligands in brain sections. The accuracy and pharmacological relevance of these methods were tested by studying the regional distribution of multiple benzodiazepine (BZ) receptors, and by analyzing the inhibitory potency of the triazolopyridazine, CL218,872, and methyl-beta-carbolinecarboxylate, two agents which discriminate between type 1 and 2 BZ receptors. The results obtained compared favorably with results previously obtained in tissue homogenates by biochemical methods. Overall, these results have practical implications. For example, quantitative autoradiography can be used to generate accurate kinetic and pharmacological displacement curves for small tissue areas. Also, since the film response curve is not linear with exposure (radioactivity X time), autoradiographs of the same sections can have relatively different density patterns depending on the time of exposure. 相似文献
68.
The location of alpha 2-adrenergic receptors has been investigated in the guinea pig kidney. We used an in vitro labeling autoradiographic technique to examine the distribution of specific [3H]clonidine binding sites with the light microscope. alpha 2-Adrenergic receptors appeared to be located predominantly on the proximal tubules. The implication of this finding for renal physiology is discussed. 相似文献
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70.
Atlas of dopamine receptor images (PET) of the human brain 总被引:2,自引:0,他引:2
Y Inoue H N Wagner D F Wong J M Links J J Frost R F Dannals A E Rosenbaum K Takeda G Di Chiro M J Kuhar 《Journal of computer assisted tomography》1985,9(1):129-140
An atlas of positron emission tomographic images of dopamine and serotonin receptor distribution in the normal and abnormal human brain has been generated using 3-N-[11C]methylspiperone as the tracer. 相似文献