Journal of pharmacobio-dynamics最新文献_第10页

Effects of a new dihydropyridine derivative, FRC-8653, on blood pressure in conscious spontaneously hypertensive rats. 新型二氢吡啶衍生物FRC-8653对有意识自发性高血压大鼠血压的影响。

Journal of pharmacobio-dynamics Pub Date : 1992-01-01 DOI: 10.1248/bpb1978.15.25

R Yoshimoto, Y Hashiguchi, H Dohmoto, M Hosono, H Iida, T Fujiyoshi, K Ikeda, Y Hayashi

{"title":"Effects of a new dihydropyridine derivative, FRC-8653, on blood pressure in conscious spontaneously hypertensive rats.","authors":"R Yoshimoto, Y Hashiguchi, H Dohmoto, M Hosono, H Iida, T Fujiyoshi, K Ikeda, Y Hayashi","doi":"10.1248/bpb1978.15.25","DOIUrl":"https://doi.org/10.1248/bpb1978.15.25","url":null,"abstract":"Antihypertensive effects of FRC-8653, a new 1,4-dihydropyridine derivative, and its combined effects with an angiotensin converting enzyme (ACE) inhibitor, a diuretic, and a beta-adrenergic blocking agent were examined in conscious spontaneously hypertensive rats (SHR). When administered intravenously to SHR (10, 30 micrograms/kg), FRC-8653 lowered blood pressure more slowly and sustained it longer than nifedipine and nicardipine. Consecutive once-daily administrations of FRC-8653 to SHR (3 mg/kg, p.o.) produced a stable reduction of blood pressure throughout the experimental period of 29 d. When blood pressure was continuously measured for 24 h in conscious unrestricted SHR, orally administered FRC-8653 produced a long-lasting reduction in blood pressure. When concomitantly used with atenolol (30 mg/kg, p.o.), the antihypertensive effect of FRC-8653 was augmented in both potency and duration. However, simultaneous administration of captopril (30 mg/kg, p.o.) or hydrochlorothiazide (2.5 mg/kg, p.o.) did not modify the antihypertensive effect of FRC-8653.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.25","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12775254","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: 11

Effects of 1-[(2-thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver regeneration and function of hepatic mitochondria in partially hepatectomized rats. 1-[(2-噻唑啉-2-基)氨基]乙酰基-4-(1,3-二硫醇-2-酰基)-2,3,4,5-四氢- 1h -1-苯并氮平-3,5-二酮盐酸(KF-14363)对部分肝切除大鼠肝脏再生和肝线粒体功能的影响。

Journal of pharmacobio-dynamics Pub Date : 1992-01-01 DOI: 10.1248/bpb1978.15.39

I Yoshitake, E Ohishi, K Kubo

{"title":"Effects of 1-[(2-thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver regeneration and function of hepatic mitochondria in partially hepatectomized rats.","authors":"I Yoshitake, E Ohishi, K Kubo","doi":"10.1248/bpb1978.15.39","DOIUrl":"https://doi.org/10.1248/bpb1978.15.39","url":null,"abstract":"Effects of 1-[(2-Thiazolin-2-yl)amino]acetyl-4-(1,3-dithiol 2-ylidene)-2,3,4,5-tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363), a hepatoprotective compound, on liver regeneration, liver nucleic acid levels, mitochondrial respiration activity and hepatic energy metabolism after partial hepatectomy (OPE) in rats were studied. The liver regeneration rate was significantly increased in rats administered 100 mg/kg of KF-14363 for 6 d as compared with the control group administered vehicle. The serum glucose level in rats administered 100 mg/kg of KF-14363 measured 3 h after OPE (OPE 3 h) was significantly higher than that in rats administered vehicle (group A) and the serum insulin level in the KF-14363 group was more than double that of group A. KF-14363 also significantly increased liver nucleic acid levels in OPE rats. In mitochondrial function experiments, KF-14363 (100 mg/kg) was orally administered 2 h after OPE. Three hours after OPE (1 h after KF-14363 administration), state 3 respiration was significantly higher in the OPE 3 h + KF-14363 group than in the OPE 3 h + water group. The adenosine diphosphate/oxygen (ADP/O) ratio was also significantly higher in the OPE 22 h (22 h after OPE) + KF-14363 group than in the OPE 22 h + water group. On hepatic energy metabolism, KF-14363 increased adenosine diphosphate and triphosphate levels. Total adenine nucleotide level in the OPE 3 h + KF-14363 group was significantly higher than that in the OPE 3 h + water group. Adenylate energy charge (AEC) was slightly decreased in the OPE 3 h + water group and significantly decreased in the OPE 22 h + water group than in the corresponding sham group.(ABSTRACT TRUNCATED AT 250 WORDS)","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.39","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12549370","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: 2

Early thrombolysis by recombinant tissue-plasminogen activator is beneficial to the ischemic myocardium. 重组组织-纤溶酶原激活剂早期溶栓对缺血心肌有利。

Journal of pharmacobio-dynamics Pub Date : 1992-01-01 DOI: 10.1248/bpb1978.15.33

K Higo, A Karasawa, K Kubo

{"title":"Early thrombolysis by recombinant tissue-plasminogen activator is beneficial to the ischemic myocardium.","authors":"K Higo, A Karasawa, K Kubo","doi":"10.1248/bpb1978.15.33","DOIUrl":"https://doi.org/10.1248/bpb1978.15.33","url":null,"abstract":"We examined the effect of coronary thrombolysis by recombinant tissue-plasminogen activator (rtPA) on infarct size using a thrombin-induced thrombosis model of open-chest anesthetized dog. Occlusive thrombus was induced by injection of thrombin (100 U) in the left anterior descending coronary artery (LAD). The intravenous infusion of rtPA (10 micrograms/kg/min) was started at 30 min (30 min-ischemia group) or at 60 min (60 min-ischemia group) after the formation of thrombus, and was continued for 30 min. Spontaneous thrombolysis was not observed in the 360 min-ischemia (vehicle-treated) group. Intravenous infusion of rtPA elicited thrombolysis within 30 min in all the dogs except in one in the 60 min-ischemia group. The infarct size was significantly reduced by rtPA-induced thrombolysis. The shorter the duration of the ischemia, the longer the effect of the drug, and the infarct size after thrombolysis was smaller in the 30 min-ischemia group than in the 60 min-ischemia group. Ischemia-induced changes in ST-segment of electrocardiogram (ECG) were significantly ameliorated after thrombolysis in both 60 min- and 30 min-ischemia group. These results suggest that early reperfusion of coronary thrombosis by rtPA is beneficial to the ischemic myocardium.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1992-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.15.33","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12775255","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: 4

Pharmacology of a phosphorus-containing novel angiotensin converting enzyme inhibitor, SQ 29 852 in anesthetized dogs. 新型含磷血管紧张素转换酶抑制剂SQ 29852在麻醉犬体内的药理作用。

Journal of pharmacobio-dynamics Pub Date : 1991-12-01 DOI: 10.1248/bpb1978.14.655

N Ohara, S Yokota, C Konishi, K Shukunobe, H Ono

{"title":"Pharmacology of a phosphorus-containing novel angiotensin converting enzyme inhibitor, SQ 29 852 in anesthetized dogs.","authors":"N Ohara, S Yokota, C Konishi, K Shukunobe, H Ono","doi":"10.1248/bpb1978.14.655","DOIUrl":"https://doi.org/10.1248/bpb1978.14.655","url":null,"abstract":"The effects of (S)-1[6-amino-2[[hydrozy(4- phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-proline (SQ 29 852), a phosphorus-containing novel angiotensin converting enzyme inhibitor (ACEI), which is synthesized aiming an ACEI with long-lasting activity and with few side effects, were studied using anesthetized dogs. SQ 29 852 was equipotent with captopril to modify blood pressure response of the animals to angiotensin I (Ang I) and bradykinin (Bdk). An intravenous infusion of SQ 29 852 at 0.1 mg/kg/min for 30 min caused a remarkable hypotension without reflex tachycardia in open-chest dogs. In these animals cardiac contractility (dP/dtmax of left ventricular pressure) appeared to be reduced by SQ 29 852 without any changes in right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP) and aortic blood flow (AoF, cardiac output). In sodium-restricted dogs, the hypotension and renal vasodilation by SQ 29 852 (at 0.01, 0.1, and 1 mg/kg, i.v.) were slightly pronounced compared with animals fed with normal diet. It is demonstrated from these results that SQ 29 852 has comparable potency with captopril to inhibit angiotensin converting enzyme (ACE) activity and as common a pharmacological profile as ACEI. SQ 29 852 may be a favorable antihypertensive agent, if its long-lasting activity and few side effects are confirmed.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.14.655","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12974103","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

Proceedings of the 10th Symposium on Microbial Sciences. Suita, July 18-19, 1991. Abstracts. 第十届微生物科学研讨会论文集。绥田，1991年7月18日至19日。摘要。

Journal of pharmacobio-dynamics Pub Date : 1991-12-01

引用次数: 0

Glycine conjugation of the substituted benzoic acids in mice: structure-metabolism relationship study II. 取代苯甲酸在小鼠中的甘氨酸偶联:结构-代谢关系研究II。

Journal of pharmacobio-dynamics Pub Date : 1991-12-01 DOI: 10.1248/bpb1978.14.671

F Kasuya, K Igarashi, M Fukui

引用次数: 11

Drug interaction between cyproheptadine and tipepidine. Effect of single and repeated administrations. 赛庚啶与替哌啶的相互作用。单次和多次给药的效果。

Journal of pharmacobio-dynamics Pub Date : 1991-12-01 DOI: 10.1248/bpb1978.14.643

T Ogiso, M Iwaki, K Yamashita, T Tanino, Y Fujii

{"title":"Drug interaction between cyproheptadine and tipepidine. Effect of single and repeated administrations.","authors":"T Ogiso, M Iwaki, K Yamashita, T Tanino, Y Fujii","doi":"10.1248/bpb1978.14.643","DOIUrl":"https://doi.org/10.1248/bpb1978.14.643","url":null,"abstract":"In order to elucidate the interaction between cyproheptadine (CPH) and tipepidine (TP), the disposition of CPH and its metabolites from plasma and the hepatic drug metabolizing enzyme activities in rats dosed singly or repeatedly were investigated. The elimination of CPH and its metabolites, desmethylCPH (DMCPH) and DMCPH-epoxide (DMCPHEPO), from plasma after a single intravenous (i.v.) administration of both CPH and TP was not significantly altered compared with that after CPH alone, although the i.v. administration of DMCPH and TP enhanced the plasma levels of DMCPHEPO. The elimination of TP from plasma was not affected by the coadministration with CPH. The single oral administration of both CPH and TP (50 mg/kg) significantly enhanced the plasma levels of CPH and DMCPH compared with those after CPH alone, consequently resulting in their delayed elimination. However, the coadministration with TP at a low dose (5 mg/kg) hardly affected the plasma decay of CPH and its metabolites. The repeated dosing of them for 7 d obscured the interactive effect. The hepatic drug-metabolizing enzyme activities, cytochrome P-450 and aminopyrine demethylase activity, were greatly increased after the repeated administration of CPH, especially showing much more increased activities after the coadministration with TP. These results suggest that the competition of hepatic oxidative metabolism between CPH or its metabolites and TP based on the depletion of the enzymes might largely be involved in the drug interaction on a single dosing of them and that the repeated dosing of them would dissolve the depletion due to their strongly inductive effect.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.14.643","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12974102","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: 0

Effects of l-menthol and dl-camphor on the penetration and hydrolysis of methyl salicylate in hairless mouse skin. l-薄荷醇和l-樟脑对无毛小鼠皮肤中水杨酸甲酯渗透和水解的影响。

Journal of pharmacobio-dynamics Pub Date : 1991-12-01 DOI: 10.1248/bpb1978.14.663

T Yano, T Kanetake, M Saita, K Noda

引用次数: 28

Effects of KF-14363 on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride. KF-14363对四氯化碳所致慢性肝损伤大鼠肝纤维化的影响。

Journal of pharmacobio-dynamics Pub Date : 1991-12-01 DOI: 10.1248/bpb1978.14.679

I Yoshitake, E Ohishi, J Sano, T Mori, K Kubo

{"title":"Effects of KF-14363 on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride.","authors":"I Yoshitake, E Ohishi, J Sano, T Mori, K Kubo","doi":"10.1248/bpb1978.14.679","DOIUrl":"https://doi.org/10.1248/bpb1978.14.679","url":null,"abstract":"The present study examined the effects of (1-[(2-thiazolin-2-yl)amino]-acetyl-4-(1,3-dithiol-2-ylidene)-2,3, 4,5- tetrahydro-1H-1-benzazepin-3,5-dione hydrochloride (KF-14363) on liver fibrosis in rats with chronic liver injury induced by carbon tetrachloride (CCl4). Liver injury in male rats was induced by repeated administration of CCl4 at 0.5 ml/kg twice a week. The progression of liver fibrosis was checked in the 4th, 6th, 8th and 10th weeks using the relative amount of hepatic 4-hydroxy proline (4-hyp) to total proteine as an index of hepatic collagen. The relative amount of hepatic 4-hyp in these rats exceeded significantly that in rats not administered CCl4 by the 4th week. This progressed in proportion to the duration of CCl4 administration. In groups concurrently administered KF-14363 at 30 and 100 mg/kg/d from the 5th or 8th week of the CCl4 administration, the relative amount of hepatic 4-hyp was found to be lower in the 10th week than at the start of the KF-14363 administration. The inhibition of liver fibrosis was also observed histopathologically. The concurrently co-administration with CCl4 or KF-14363 at 30 and 100 mg/kg for 2 or 5 weeks inhibited the increases in serum transaminases and alkaline phosphatase induced by CCl4. The results show that KF-14363 inhibits liver fibrosis in a dose dependent fashion in rats with progressive liver injury.","PeriodicalId":16743,"journal":{"name":"Journal of pharmacobio-dynamics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"1991-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1248/bpb1978.14.679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12974106","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: 10

Pharmacokinetics of haloperidol decanoate in rats. 癸酸氟哌啶醇在大鼠体内的药动学。

Journal of pharmacobio-dynamics Pub Date : 1991-11-01 DOI: 10.1248/bpb1978.14.615

Y Oh-e, H Miyazaki, Y Matsunaga, M Hashimoto

引用次数: 13