Journal of pharmacobio-dynamics最新文献_第9页

Relationship between lipophilicity and binding affinity with human serum albumin for penicillin and cephem antibiotics. 青霉素和头孢类抗生素的亲脂性及其与人血清白蛋白结合亲和力的关系。

Journal of pharmacobio-dynamics Pub Date : 1992-03-01 DOI: 10.1248/bpb1978.15.99

T Terasaki, H Nouda, A Tsuji

{"title":"Relationship between lipophilicity and binding affinity with human serum albumin for penicillin and cephem antibiotics.","authors":"T Terasaki, H Nouda, A Tsuji","doi":"10.1248/bpb1978.15.99","DOIUrl":"https://doi.org/10.1248/bpb1978.15.99","url":null,"abstract":"Relationship between structure and binding affinity to human serum albumin (HSA) has been studied for penicillin and cephem antibiotics. For penicillin analogs, a good correlation between the apparent affinity constants, Kapp, for HSA binding and the partition coefficient, Papp, determined in isobutyl alcohol-pH 7.4 phosphate buffer system was observed, indicating that the hydrophobic interaction of 6-substituent of penicillins with amino acid of HSA would play an important role for the binding. However, no correlation between the Kapp and Papp values was observed for cephem antibiotics. Mutual competitive displacement effects were demonstrated for the primary binding sites of cephalothin, cefazolin, cefotetan and cefatrizine, suggesting the presence of a common binding region in HSA among these cephem antibiotics examined. Significant differences were observed for the Kapp value among cephems having the same 3-substitute of N-methylthiotetrazole in the molecule, i.e., cefpiramide, cefotetan, cefoperazone, cefamandole, cefmenoxime, cefmetazole and cefbuperazone, suggesting that 7-substitute of cephem would play an important role for the binding with HSA. Moreover, comparing the binding affinity and the structure of 3-substitute for cephems, all of the analogs having a heterocycle bind strongly with HSA in spite of their low lipophilicity. These observations suggest that an interaction between heterocycle at the position 3 and HSA would contribute to an additional binding force for the binding of cephem antibiotics to HSA.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 3","pages":"99-106"},"PeriodicalIF":0.0,"publicationDate":"1992-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.99","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12791651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 14

Proceedings of the 17th Symposium on Progress in Organic Reactions and Syntheses. Fukuoka, November 7-8, 1991. Abstracts. 第十七届有机反应与合成学术研讨会论文集。福冈，1991年11月7日至8日。摘要。

Journal of pharmacobio-dynamics Pub Date : 1992-03-01

引用次数: 0

Comparative effects of chloroflavone congeners as inducers of hepatic microsomal monooxygenases in rats. 氯黄酮同源物诱导大鼠肝微粒体单加氧酶的比较作用。

Journal of pharmacobio-dynamics Pub Date : 1992-02-01 DOI: 10.1248/bpb1978.15.59

K Yamamoto, S Kato

{"title":"Comparative effects of chloroflavone congeners as inducers of hepatic microsomal monooxygenases in rats.","authors":"K Yamamoto, S Kato","doi":"10.1248/bpb1978.15.59","DOIUrl":"https://doi.org/10.1248/bpb1978.15.59","url":null,"abstract":"The inductive effects of pretreatment with 10 synthetic chloroflavone isomers and congeners (80 mg/kg/d for 3 d, i.p.) on hepatic microsomal monooxygenases were examined with male Wistar rats. All chloroflavone congeners, except 3'-chloroflavone (CF), significantly increased (1.2- to 2-fold) the content of total cytochrome P-450 (P-450s) in microsomes. The effects of these congeners were evaluated based on the activities of microsomal aminopyrine N-demethylase, aniline hydroxylase and scoparone (6,7-dimethoxycoumarin) O-demethylase, and the CO difference spectrum and sodium dodecyl sulfate-gel electrophoretogram of cytochrome P-450s. The results were compared with those of phenobarbital (PB), 3-methylcholanthrene (MC) and PB plus MC. Based mainly on effects on the CO difference spectrum and ratio of the two O-demethylase activities of scoparone, 2'-CF and 2',4'-dichloroflavone (DCF) were categorized as the PB-type, 4'-CF and 6,8-DCF as the MC-type, 3',6-DCF and 3',5',6-trichloroflavone as weak MC-type, and 6-CF and 2',6-DCF as mixed (PB plus MC)-type inducers. A comparison of chloroflavone isomers and congeners indicated that (1) the presence of the 2'-chloro substituent of the flavone system is a minimal requirement for exhibiting the PB-type effect, (2) the absence of the 2'-chloro substituent is possibly that for exhibiting the MC-type effect and (3) the induction potencies by individual chloroflavone congeners may not be related to the degrees of chlorination.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 2","pages":"59-66"},"PeriodicalIF":0.0,"publicationDate":"1992-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.59","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12575222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

YM-14673, a new thyrotropin-releasing hormone analog, augments long-term potentiation in the mossy fiber-CA3 system of guinea pig hippocampal slices. YM-14673是一种新的促甲状腺激素释放激素类似物，可增强豚鼠海马鳞片苔藓纤维- ca3系统的长期增强。

Journal of pharmacobio-dynamics Pub Date : 1992-02-01 DOI: 10.1248/bpb1978.15.75

K Ishihara, H Katsuki, M Sugimura, M Satoh

引用次数: 9

Phospholipid metabolism in platelets from stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats. 卒中易发自发性高血压大鼠和Wistar京都大鼠血小板磷脂代谢。

Journal of pharmacobio-dynamics Pub Date : 1992-02-01 DOI: 10.1248/bpb1978.15.49

M Ikeda, T Onda, T Mitsubori, K Umegaki, I Tomita, T Tomita

{"title":"Phospholipid metabolism in platelets from stroke-prone spontaneously hypertensive rats and Wistar Kyoto rats.","authors":"M Ikeda, T Onda, T Mitsubori, K Umegaki, I Tomita, T Tomita","doi":"10.1248/bpb1978.15.49","DOIUrl":"https://doi.org/10.1248/bpb1978.15.49","url":null,"abstract":"Platelets from stroke-prone spontaneously hypertensive rats (SHRSP) show severe hypofunctions accompanied by defective protein (P47) phosphorylation. To examine the mechanism of platelet hypofunctions, phospholipid metabolism in SHRSP was compared with that in Wistar Kyoto rats (WKY). Phosphatidylinositol (PI) content was 20% less in SHRSP than in WKY, but no changes were observed in other phospholipids. Incorporation of [3H]-arachidonic acid (AA) into PI and phosphatidylethanolamine (PE) was 12% and 11% lower, and that into phosphatidylcholine (PC) was 6% higher in SHRSP than in WKY. Thrombin-induced diacylglycerol and phosphatidic acid formation were similar in both groups of platelets. Thrombin-induced release of [14C]-AA from the labeled platelets and its metabolism to eicosanoids occurred at similar rates. These results suggest that reduced formation of diacylglycerol, an activator of protein kinase C (PKC), does not cause defective phosphorylation of P47, a substrate of PKC, in SHRSP. However it remains unclear how the lower PI content and the altered distribution of AA in PC and PE is related to SHRSP platelet hypofunctions.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 2","pages":"49-57"},"PeriodicalIF":0.0,"publicationDate":"1992-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.49","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12502126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

An application of microdialysis to drug tissue distribution study: in vivo evidence for free-ligand hypothesis and tissue binding of beta-lactam antibiotics in interstitial fluids. 微透析在药物组织分布研究中的应用:游离配体假说的体内证据和-内酰胺类抗生素在间质液中的组织结合。

Journal of pharmacobio-dynamics Pub Date : 1992-02-01 DOI: 10.1248/bpb1978.15.79

Y DeGuchi, T Terasaki, H Yamada, A Tsuji

{"title":"An application of microdialysis to drug tissue distribution study: in vivo evidence for free-ligand hypothesis and tissue binding of beta-lactam antibiotics in interstitial fluids.","authors":"Y DeGuchi, T Terasaki, H Yamada, A Tsuji","doi":"10.1248/bpb1978.15.79","DOIUrl":"https://doi.org/10.1248/bpb1978.15.79","url":null,"abstract":"To prove the free-ligand hypothesis for extravascular equilibration and tissue binding mechanism of beta-lactam antibiotics, the microdialysis technique has been employed for the lung, the muscle and the liver in rats. Cefminox, a cephem antibiotic, and SY5555, a new penem antibiotic, were used in the present study. During the constant infusion of each antibiotic with simultaneous infusion of antipyrine, the microdialysis studies were performed and the dialysate concentrations were determined. The dialysate concentration was extrapolated to the in vivo unbound concentration in tissue interstitial fluids (Cisf,u) according to the extrapolation method which was derived from the clearance concept. This extrapolation method incorporates the effective dialysis coefficient of a reference compound, antipyrine, which is used to correct the difference between in vivo and in vitro permeabilities of microdialysis fiber. The values of Cisf,u values for cefminox and SY5555 in the lung, muscle and liver were close to the unbound concentrations in the venous plasma leaving these organs. Furthermore, good coincidences were obtained between the unbound concentrations of SY5555 in lung and muscle interstitial fluids estimated from the total concentrations in homogenized tissues and those extrapolated by the microdialysis studies. Consequently, the present microdialysis studies provided the in vivo evidence that 1) the free-ligand hypothesis for extravascular equilibration of beta-lactam antibiotics is true, and that 2) beta-lactam antibiotics are restricted in the interstitial space in a noneliminating organ and bind only with albumin existing in this space.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 2","pages":"79-89"},"PeriodicalIF":0.0,"publicationDate":"1992-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.79","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12576409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 50

The biological fate of sodium prasterone sulfate after vaginal administration. I. Absorption and excretion in rats. 阴道给药后硫酸普酮钠的生物学命运。1 .大鼠吸收排泄。

Journal of pharmacobio-dynamics Pub Date : 1992-02-01 DOI: 10.1248/bpb1978.15.67

M Sakaguchi, T Sakai, Y Adachi, T Kawashima, N Awata

引用次数: 7

Diabetic state-induced modification of insulin-stimulated, glucose uptake into and kinase activity in, the diaphragm muscle of genetically diabetic KK-CAy mice. 糖尿病状态诱导的胰岛素刺激、葡萄糖摄取和遗传性糖尿病KK-CAy小鼠膈肌激酶活性的改变。

Journal of pharmacobio-dynamics Pub Date : 1992-01-01 DOI: 10.1248/bpb1978.15.17

M Kimura, T Naitoh, S Kobayashi, I Kimura

{"title":"Diabetic state-induced modification of insulin-stimulated, glucose uptake into and kinase activity in, the diaphragm muscle of genetically diabetic KK-CAy mice.","authors":"M Kimura, T Naitoh, S Kobayashi, I Kimura","doi":"10.1248/bpb1978.15.17","DOIUrl":"https://doi.org/10.1248/bpb1978.15.17","url":null,"abstract":"The effect of insulin on glucose and 2-deoxyglucose uptake into isolated diaphragm was investigated in genetically diabetic KK-CAy mice, and in part in alloxan-treated mice. Concentration-response curves of insulin for glucose uptake (8.3 mM in vitro) for 1 h were shifted to the left in two kinds of diabetic model mice. Insulin-stimulated glucose uptake was biphasic; it was high 1 week, and returned to the normal level 4 weeks, after alloxan injection despite high blood glucose levels. Insulin-stimulated glucose uptake was the same at higher glucose levels (25 mM) as at 8.3 mM glucose for 1 h, despite an increase in basal glucose uptake (without insulin) in KK-CAy mice. Insulin-receptor kinase activity in diabetic KK-CAy mouse diaphragm also changed biphasically as the glucose concentration increased: an increase at 8.3 mM, but no increase at 16.7 mM or 25.0 mM glucose for 3 h-pretreatment including 1 h-insulin treatment. These results suggest that although the initial state of diabetes enhances insulin action, the prolonged hyperglycemia rather suppressed the insulin action in vivo.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 1","pages":"17-23"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.17","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12492935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Interaction mode of dicumarol and its derivatives with human serum albumin, alpha 1-acid glycoprotein and asialo alpha 1-acid glycoprotein. 双豆醇及其衍生物与人血清白蛋白、α 1-酸性糖蛋白和亚洲鱼α 1-酸性糖蛋白的相互作用模式。

Journal of pharmacobio-dynamics Pub Date : 1992-01-01 DOI: 10.1248/bpb1978.15.7

M H Rahman, T Miyoshi, K Sukimoto, A Takadate, M Otagiri

{"title":"Interaction mode of dicumarol and its derivatives with human serum albumin, alpha 1-acid glycoprotein and asialo alpha 1-acid glycoprotein.","authors":"M H Rahman, T Miyoshi, K Sukimoto, A Takadate, M Otagiri","doi":"10.1248/bpb1978.15.7","DOIUrl":"https://doi.org/10.1248/bpb1978.15.7","url":null,"abstract":"The interaction of dicumarol and its seven other derivatives with human serum albumin (HSA), alpha 1-acid glycoprotein (AGP) and desialylatedAGP (asialoAGP) has been investigated by circular dichroism (CD) and fluorescence. The binding parameters of dicumarol and its derivatives obtained from fluorescence almost agreed with those obtained from CD. The binding data indicated that the total binding affinities (nK) to HSA were higher than the binding affinities to AGP and asialoAGP. Hydrophobic interaction was the driving force for the binding to all the three proteins and nK values in the binding process were found to be increased with the increase of hydrophobicity of the compound. This was evidenced by the attempts taken to correlate binding affinities with partition coefficients. Both electrostatic and van der Waals interactions were not found to play any significant role in the binding of these compounds to any of these three proteins. However, in case of the AGP and asialoAGP binding, apart from the hydrophobic interaction, some other forces may be involved as evidenced from the experimental data. Binding was exothermic, entropy driven and spontaneous. The change of enthalpy (delta H degree) was compensated for by the change in entropy (delta S degree). Relative contribution of hydrophobic interactions in the binding of these compounds to HSA was higher than to AGP or asialoAGP. Sialic acid was not found to impart any significant role in the binding of these compounds to AGP.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":"15 1","pages":"7-16"},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12549371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

Nasal absorption of digoxin in rats. 地高辛在大鼠体内的鼻腔吸收。

Journal of pharmacobio-dynamics Pub Date : 1992-01-01 DOI: 10.1248/bpb1978.15.1

Y Kato, N Yagi, S Yamada, M Sato, R Kimura

引用次数: 3