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991.
Rosmarinic acid and caffeic acid produce antidepressive-like effect in the forced swimming test in mice 总被引:9,自引:0,他引:9
Takeda H Tsuji M Inazu M Egashira T Matsumiya T 《European journal of pharmacology》2002,449(3):261-267
We previously showed that rosmarinic acid from the leaves of Perilla frutescens Britton var. acuta Kudo (Perillae Herba) has antidepressive-like activity. The aim of the present study was to examine (i) whether caffeic acid, a major metabolite of rosmarinic acid, also has antidepressive-like activity, and (ii) whether these substances inhibit either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity. Rosmarinic acid (2 mg/kg, i.p.) and caffeic acid (4 mg/kg, i.p.) each significantly reduced the duration of immobility in the forced swimming test in mice. In contrast, neither substance, at doses that produced a significant reduction in the immobile response in the forced swimming test, affected spontaneous motor activity. These results indicate that, like rosmarinic acid, caffeic acid also possesses antidepressive-like activity. In neuropharmacological studies, neither rosmarinic acid (10 x (-9)-10 x (-3) M) nor caffeic acid (10 x (-9)-10 x (-3) M) affected either the uptake of monoamines to synaptosomes or mitochondrial monoamine oxidase activity in the mouse brain. These results suggest that both caffeic acid and rosmarinic acid may produce antidepressive-like activity via some mechanism(s) other than the inhibition of monoamine transporters and monoamine oxidase. 相似文献
992.
Fukatsu K Uchikawa O Kawada M Yamano T Yamashita M Kato K Hirai K Hinuma S Miyamoto M Ohkawa S 《Journal of medicinal chemistry》2002,45(19):4212-4221
We synthesized a novel series of benzocycloalkene derivatives and evaluated their binding affinities to melatonin receptors. To control the spatial position of the amide group, one of the important pharmacophores, we incorporated an endo double bond, an exo double bond (E- and Z-configurations), and a chiral center (R- and S-configurations) at position 1. The indan derivatives with the S-configuration at position 1 were the most promising in terms of potency and selectivity for the human melatonin receptor (MT(1) site), while compounds with the R-configuration showed little potential. Our next attempt was to investigate the most favorable conformation of the methoxy group, the other important pharmacophore for binding to the MT(1) receptor. The introduction of a methyl group at position 5 of the indene ring conserved affinity; however, at position 7, it caused a decrease in affinity. These results suggested that the substitution at position 7 forced the methoxy group to adopt an unfavorable orientation. The optimization of the condensed ring size and substituents led to (S)-8d [(S)-N-[2-(2,3-dihydro-6-methoxy-1H-inden-1-yl)ethyl]propionamide], which had high affinity for the human MT(1) receptor (K(i) = 0.041 nM) but no significant affinity for the hamster MT(3)receptor (K(i) = 3570 nM). In addition, a practical synthetic method of chiral N-[2-(2,3-dihydro-1H-inden-1-yl)ethyl]alkanamides employing asymmetric hydrogenation with (S)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl-Ru has been established. 相似文献
993.
Hokama N Hobara N Sakai M Kameya H Ohshiro S Sakanashi M 《The Journal of pharmacy and pharmacology》2002,54(6):821-825
The effect of two kinds of 1,4-dihydropyridine calcium-channel blockers, nicardipine hydrochloride and nifedipine, on the disposition of carvedilol, was studied in rats. Blood samples were assayed for carvedilol levels using solid-phase extraction and high-performance liquid chromatography. The plasma carvedilol concentration was found to be significantly higher, and the area under the concentration-time curve up to 24 h (AUC0-->24) was 6.7 and 3.0 times higher after simultaneous oral administration of 20 mg kg(-1) carvedilol with 40 mg kg(-1) nicardipine hydrochloride, or with 40 mg kg(-1) nifedipine, respectively, than after administration of carvedilol alone. The pharmacokinetic interaction between carvedilol and dihydropyridine calcium-channel blockers is thought to be attributable to vasodilator-induced changes in hepatic first-pass metabolism, inhibition in the absorption barrier by P-glycoprotein and in the metabolism of carvedilol. 相似文献
994.
995.
A novel alkaline phosphatase (S-ALP) was found in the culture filtrate of Streptomyces hiroshimensis IFO 12785. Purification was achieved on Sephadex G-75 column, palmitoylated gauze column, and Superdex 75 HR column chromatographies. The molecular weight of S-ALP was estimated to be 14200 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The isoelectric point is 9.2. S-ALP had maximum enzyme activity at pH 9.5. S-ALP efficiently catalyzed both p-nitrophenyl phosphate and p-nitrophenyl phosphorylcholine substrates, particularly the latter. The N-terminal amino acid sequence (25 residues) of S-ALP was 60 to 72% identical to that of Streptomyces subtilisin inhibitor-like proteins. S-ALP exhibited trypsin inhibition in addition to a strong inhibition of subtilisin. 相似文献
996.
Kato R Ooi K Takeda K Mashimo K Fujimura Y Kusumoto M Ueno K 《Drug metabolism and pharmacokinetics》2002,17(4):363-366
The effect of calcium polycarbophil on the absorption of cefdinir, cephalosporin derivative, was evaluated in both in vitro and in vivo studies. In the in vitro study, the release of cefdinir from a cellulose membrane in the presence or absence of metal cations was measured using the dissolution test procedure. In the in vivo study, volunteers and a randomized crossover design with two phases were used. In the first phase, the volunteers received 200 mg of cefdinir alone (Study 1); in the other phase, they received 200 mg of cefdinir and 1200 mg of fine calcium polycarbophil granules concomitantly (Study 2). The cefdinir concentrations in the samples or serum were measured by an UV-VIS spectrophotometer or high-performance liquid chromatography. Release in the presence of iron ions was slower than that in the absence of metal ions, however no difference was observed between release in the presence of calcium ions and that in the absence of metal ions. No difference was observed in AUC(0-10), C(max) and t(max) between Study 1 and Study 2. The absorption of cefdinir was not affected by co-administration of calcium polycarbophil. Moreover, the in vitro study on the release of drugs from a cellulose membrane may predict the absorption of a drug caused by the formation of chelate complexes between the drug and metal ions. 相似文献
997.
Morikawa T Matsuda H Toguchida I Ueda K Yoshikawa M 《Journal of natural products》2002,65(10):1468-1474
The 80% aqueous acetone extract and the ethyl acetate-soluble portion from the dried fruit of Alpinia oxyphylla MIQUEL were found to show inhibitory effects on nitric oxide production in lipopolysaccharide-activated macrophages and antigen-induced degranulation in RBL-2H3 cells. A new eudesmane-type sesquiterpene, oxyphyllol A, and two eremophilane-type sesquiterpenes, oxyphyllols B and C, were isolated from the ethyl acetate-soluble portion, together with 16 known constituents. The absolute stereostructures of oxyphyllols A, B, and C were determined on the basis of chemical and physicochemical evidence. The effects of isolated components on nitric oxide production were examined, and nine constituents including oxyphyllol A and nootkatone were found to show inhibitory activity. On the other hand, five constituents inhibited the release of beta-hexosaminidase from RBL-2H3 cells. 相似文献
998.
Bumetanide-induced enlargement of the intercellular space in the stria vascularis requires an active Na+-K+-ATPase 总被引:2,自引:0,他引:2
Azuma H Takeuchi S Higashiyama K Ando M Kakigi A Nakahira M Yamakawa K Takeda T 《Acta oto-laryngologica》2002,122(8):816-821
OBJECTIVE: Loop diuretics such as bumetanide and furosemide cause an acute enlargement of the intrastrial space of the stria vascularis, with an associated decline in the endocochlear DC potential (EP). The aim of this study was to determine the role played by the Na+-K+-ATPase in the bumetanide-induced enlargement of the intrastrial space, and to examine the importance of the balance between the activities of the Na+-K+-2Cl- cotransporter and the Na+-K+-ATPase to the physiological function of the stria vascularis. MATERIAL AND METHODS: Albino guinea pigs were used in experiments involving perilymphatic perfusion, EP measurement and electron microscopy. The effects of bumetanide on the stria vascularis were examined following inhibition of the Na+-K+-ATPase by ouabain. Ouabain was administered to the perfusate and, when the EP reached 0 mV, both ouabain and bumetanide were administered. RESULTS: Although there was no enlargement of the intrastrial space, vacuoles were apparent in marginal cells. The vacuolar change in marginal cells was similar to that caused by ouabain alone. CONCLUSION: This study indicates that the enlargement of the intrastrial space requires not only the blockade of the Na+-K+-2Cl- cotransporter but also normal activity of the Na+-K+-ATPase, and suggests that the bumetanide-induced enlargement of the intrastrial space resulted from the imbalance between the activities of the Na+-K+-2Cl- cotransporter and the Na+-K+-ATPase. 相似文献
999.
We have identified a novel form of cardiac myocyte enlargement in nonmuscle myosin heavy chain II-B (NMHC II-B) ablated mice, based on a partial failure in cytokinesis. In contrast to most cells, cardiac myocytes lack NMHC II-A, and ablation of NMHC II-B results in a heart with 70% fewer myocytes at embryonic day 14.5 (E14.5) than control mice (B+/B- and B+/B+). In addition, B-/B- cardiac myocytes show a marked increase in binucleation at E12.5, reflecting the occurrence of karyokinesis in the absence of cytokinesis. An increase in binucleation and cell size is also found in hypomorphic, homozygous mice harboring a single amino acid mutation (R709C) in the gene encoding NMHC II-B. The nonmyocytes in B-/B- hearts and homozygous mutant hearts, all of which contain NMHC II-A, do not show either of these abnormalities. B-/B- cardiac myocytes at E14.5 show a decreased bromodeoxyuridine (BrdU) labeling index compared with controls, consistent with the decrease in myocyte proliferation. This decreased BrdU labeling is not seen in nonmyocyte cells in the heart. In addition to these changes, both B-/B- mice as well as homozygous mutated mice show an increase in cyclin D2 and D3 reflecting an abnormality in earlier steps in the cell cycle. Whereas cardiac myocytes completely ablated for NMHC II-B show enlargement and binucleation, mice expressing as little as 6% of the normal amount of wild-type NMHC II-B in the heart do not show these abnormalities. 相似文献
1000.