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Propofol for patients with Huntington''s chorea? 总被引:2,自引:0,他引:2
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The perception of moving objects and our successful interaction with them entail that the visual system integrates shape and motion information about objects. However, neuroimaging studies have implicated different human brain regions in the analysis of visual motion (medial temporal cortex; MT/MST) and shape (lateral occipital complex; LOC), consistent with traditional approaches in visual processing that attribute shape and motion processing to anatomically and functionally separable neural mechanisms. Here we demonstrate object-selective fMRI responses (higher responses for intact than for scrambled images of objects) in MT/MST, and especially in a ventral subregion of MT/MST, suggesting that human brain regions involved mainly in the processing of visual motion are also engaged in the analysis of object shape. 相似文献
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P D Williams M G Bock R D Tung V M Garsky D S Perlow J M Erb G F Lundell N P Gould W L Whitter J B Hoffman 《Journal of medicinal chemistry》1992,35(21):3905-3918
A new structural class of cyclic hexapeptide oxytocin antagonists derived from Streptomyces silvensis and typified by L-365,209 (cyclo-[L-prolyl1-D-phenylalanyl2-L- isoleucyl3-D-dehydropiperazyl4-L-dehydroperazyl5-D-(N- methyl)phenylalanyl6]) was recently reported. In this paper we further delineate the structure-activity profile for this new class by systematic study of L-365,209 analogs obtained by total synthesis. The optimal combination of cyclic amino acid ring sizes at positions 1, 4, and 5 and the role of the N-alkyl substituent at position 6 was elucidated. The lipophilic amino acids at positions 2 and 3 and the unusual amino acid D-dehydropiperazic acid at position 4 were found to be the most critical residues for obtaining good oxytocin receptor affinity. Analogs containing a basic side chain at the less critical 5- and 6-positions maintained good receptor affinity and also had useful levels of water solubility for intravenous formulation. By combining potency- and solubility-enhancing substitutions, several analogs were identified that have the desired combination of properties in vitro (22, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L-pipeco lyl-D- histidyl]; 25, cyclo-[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L -pipecolyl-D- histidyl]; 26, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-dehydropiperazyl-L-++ pipecolyl-D-histidyl]; 33, cyclo-[L-prolyl-D-tryptophanyl-L-isoleucyl-D-pipecolyl-L- piperazinylcarboxy-D-(N-methyl)phenylalanyl]; 34, cyclo-[L-prolyl-D-phenylalanyl-L-isoleucyl-D-dehydropiperazyl-L-or nithyl- D-(N-methyl)phenylalanyl]). In general, this class exhibited good selectivity for binding to the oxytocin receptor versus the arginine vasopressin V1a and V2 receptor subtypes, although increased V2 receptor affinity was observed in one case (32, cyclo[L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl-L- lysyl-D-(N- methyl)phenylalanyl]). Unexpectedly, compound 33 was found to stimulate contractions of the isolated rat uterus via activation of the uterine bradykinin receptor. Compounds 22, 25, 26, 33, and 34 were found to be potent antagonists of oxytocin-stimulated contraction of the rat uterus in vitro and in vivo. Compounds 22 and 25 were additionally characterized as potent antagonists of oxytocin-stimulated uterine contractions in the near-term pregnant rhesus monkey. These studies thus demonstrate the selectivity and efficacy of certain members of this novel class of antagonists and suggest their use as pharmacological tools in further defining the role of oxytocin in both term and preterm labor. 相似文献
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