Acta pharmacologica et toxicologica最新文献_第7页

Pharmacodynamics and toxicology of fenflumizole, a new non-steroidal anti-inflammatory imidazole derivative. 新型非甾体抗炎咪唑衍生物芬氟唑的药效学和毒理学研究。

Acta pharmacologica et toxicologica Pub Date : 1983-10-01 DOI: 10.1111/j.1600-0773.1983.tb03425.x

T Corell, G Hasselmann

{"title":"Pharmacodynamics and toxicology of fenflumizole, a new non-steroidal anti-inflammatory imidazole derivative.","authors":"T Corell, G Hasselmann","doi":"10.1111/j.1600-0773.1983.tb03425.x","DOIUrl":"https://doi.org/10.1111/j.1600-0773.1983.tb03425.x","url":null,"abstract":"Fenflumizole, (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl) imidazole), a new non-steroidal anti-inflammatory agent, was investigated for anti-inflammatory, analgesic and anti-pyretic activity in experimental animals. Comparison was made to other non-steroidal anti-phlogistics. Furthermore, general pharmacodynamics and toxicity of fenflumizole was studied. Fenflumizole was comparable to or weaker than indomethacin in models of acute inflammation (carrageenin paw oedema and pleurisy, rats, ultraviolet erythema, guinea-pigs) and stronger than indomethacin as an analgesic (writhing, mice). As an antipyretic agent (arachidonic acid pyresis, rats) fenflumizole was 3 times weaker than indomethacin. The acute gastro-ulcerogenicity and toxicity of fenflumizole was low as compared to reference drugs. No untoward activity of fenflumizole on respiratory and circulatory systems was observed in rabbits and dogs. Fenflumizole is a potential new therapeutic agent with anti-inflammatory, analgesic and anti-pyretic activities comparable to other anti-phlogistics but with reduced side effects.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"53 4","pages":"288-96"},"PeriodicalIF":0.0,"publicationDate":"1983-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0773.1983.tb03425.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17705571","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: 21

Hepatotoxicity of hornet's venom sac extract, after repeated in vivo and in vitro envenomation. 大黄蜂毒囊提取物经体内、体外反复毒化后的肝毒性研究。

Acta pharmacologica et toxicologica Pub Date : 1983-10-01 DOI: 10.1111/j.1600-0773.1983.tb03428.x

M G Neuman, J Eshchar, D Cotariu, J S Ishay, L Bar-Nea

{"title":"Hepatotoxicity of hornet's venom sac extract, after repeated in vivo and in vitro envenomation.","authors":"M G Neuman, J Eshchar, D Cotariu, J S Ishay, L Bar-Nea","doi":"10.1111/j.1600-0773.1983.tb03428.x","DOIUrl":"https://doi.org/10.1111/j.1600-0773.1983.tb03428.x","url":null,"abstract":"The activity of some enzymes involved in hepatic function was measured in rats, in vivo, after one week's repeated envenomation with Hornet's (Vespa orientalis) venom sac extract (VSE) and in vitro in monolayers of tissue culture of rat hepatocytes treated with VSE. The maximal serum enzymatic changes observed in vivo were significant: twenty fold rise of alkaline phosphatase (ALP), a 7-8 fold rise of aspartate aminotransferase (AST) and a 4-5 fold rise in alanine aminotransferase (ALP) activity. Also 2-3x increases of both serum lactic dehydrogenase (LDH) and creatine phosphokinase (CPK) were noted. The maximal in vitro changes were observed after six days of daily envenomation. There were five fold rises of the activity of AST in the medium, as well as of two-three fold rises of ALT, ALP and LDH. These changes suggest that Hornet's VSE induces enzymatic changes in the liver after prolonged, repeated exposures. They also exclude a general effect, like shock, that might possibly occur in the intact animal, as the cause of the demonstrated hepatic damage.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"53 4","pages":"314-9"},"PeriodicalIF":0.0,"publicationDate":"1983-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0773.1983.tb03428.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17705573","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: 15

Fenflumizole: interactions with the arachidonic acid cascade. 芬氟唑:与花生四烯酸级联的相互作用。

Acta pharmacologica et toxicologica Pub Date : 1983-10-01 DOI: 10.1111/j.1600-0773.1983.tb03426.x

T Corell, G Hasselmann, J Splawinski, B Wojtaszek

{"title":"Fenflumizole: interactions with the arachidonic acid cascade.","authors":"T Corell, G Hasselmann, J Splawinski, B Wojtaszek","doi":"10.1111/j.1600-0773.1983.tb03426.x","DOIUrl":"https://doi.org/10.1111/j.1600-0773.1983.tb03426.x","url":null,"abstract":"Fenflumizole (2-(2,4-difluorophenyl)-4,5-bis(4-methoxyphenyl)imidazole), a new non-steroidal anti-inflammatory agent, was investigated for interference with cyclo-oxygenase activity in vivo, ex vivo and in vitro in comparison with indomethacin (and aspirin). Fenflumizole was comparable to indomethacin ex vivo in inhibition of thromboxane (TX)A2 production in rabbit platelets and inhibition of prostaglandin (PG)I2 (approximately prostacyclin) generation in rabbit mesenteric arteries and in vivo as an inhibitor of PGE2 formation in inflammatory exudates in rats. Fenflumizole was 18 times less active than indomethacin in inhibition of PGE2 synthesis in vitro and 170 times weaker as an inhibitor of PGI2 generation in the rat stomach mucosa ex vivo. Fenflumizole was 20-50 times more potent than indomethacin in vivo in inhibition of arachidonic acid induced bronchoconstriction in guinea-pigs, in inhibition of platelet aggregation on tendons superfused with blood from rabbits and in vitro in inhibition of aggregation of human and rabbit platelets. Neither fenflumizole nor indomethacin inhibited TXA2-synthetase in vitro. Aspirin-when tested-was less potent than fenflumizole and indomethacin. It is concluded that fenflumizole is a potent cyclo-oxygenase inhibitor. The very potent activity of fenflumizole against platelet aggregation and bronchoconstriction suggests a selectivity in the mode of action. The weak inhibition of gastric PGI2 generation may account for the previously observed weak gastro-ulcerogenicity of fenflumizole.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"53 4","pages":"297-303"},"PeriodicalIF":0.0,"publicationDate":"1983-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0773.1983.tb03426.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17477219","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: 15

Effects of trifluoperazine on beta-adrenergic responses of rat papillary muscle: related to calmodulin? 三氟拉嗪对大鼠乳头肌β -肾上腺素能反应的影响:与钙调素有关?

Acta pharmacologica et toxicologica Pub Date : 1983-10-01 DOI: 10.1111/j.1600-0773.1983.tb03422.x

H Aass, T Skomedal, J B Osnes

{"title":"Effects of trifluoperazine on beta-adrenergic responses of rat papillary muscle: related to calmodulin?","authors":"H Aass, T Skomedal, J B Osnes","doi":"10.1111/j.1600-0773.1983.tb03422.x","DOIUrl":"https://doi.org/10.1111/j.1600-0773.1983.tb03422.x","url":null,"abstract":"The beta-adrenergic stimulation of cardiac contraction and relaxation is related to an augmented Ca++ oscillation mediated by cAMP. This Ca++ mobilization may secondarily involve calmodulin in a way modulating the mechanical responses. We tested this possibility by studying interferences of trifluoperazine (which is able to block Ca++-calmodulin) with beta-adrenergic responses in rat heart papillary muscles. Trifluoperazine up to 10(-5) mol/l did not change the basal function. 10(-5) mol/l trifluoperazine augmented the contractile response to isoprenaline above 10(-7) mol/l. The inotropic effects of isoprenaline below 10(-7) mol/l and of the partial beta-agonist prenalterol were not influenced by trifluoperazine. 10(-5) mol/l trifluoperazine attenuated the stimulation of initial relaxation by isoprenaline in the entire concentration range. Thus this beta-adrenergic response was more sensitive to trifluoperazine than the contractile response. But trifluoperazine only slightly and non-significantly attenuated the stimulation of initial relaxation by prenalterol. From experiments on broken cell preparations the present results can be explained in terms of calmodulin blockade and thus inhibition of Ca++ efflux across the sarcolemma and of Ca++ uptake by the sarcoplasmic reticulum. Trifluoperazine effects unrelated to calmodulin can hardly account for the results. Thus a full beta-agonist can apparently mobilize enough Ca++ to activate calmodulin systems important for the final effects on the contraction-relaxation cycle.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"53 4","pages":"265-74"},"PeriodicalIF":0.0,"publicationDate":"1983-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0773.1983.tb03422.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17205816","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

Activation of factor XII in human plasma: protection by benzamidine of the cofactor function of high molecular weight kininogen. 人血浆中XII因子的活化:苯并脒对高分子量激肽原辅助因子功能的保护作用。

Acta pharmacologica et toxicologica Pub Date : 1983-10-01 DOI: 10.1111/j.1600-0773.1983.tb03433.x

K Briseid, H T Johansen

{"title":"Activation of factor XII in human plasma: protection by benzamidine of the cofactor function of high molecular weight kininogen.","authors":"K Briseid, H T Johansen","doi":"10.1111/j.1600-0773.1983.tb03433.x","DOIUrl":"https://doi.org/10.1111/j.1600-0773.1983.tb03433.x","url":null,"abstract":"By incubation of human citrated plasma with acetone 25% v/v kallikrein inhibitors were destroyed and prekallikrein activated to kallikrein. When the incubation was carried out in the presence of benzamidine 7 mM, the cofactor capacity of high molecular weight kininogen (HMrK) was protected against destruction by a serine protease which was not plasma kallikrein. By analogy with studies in rat plasma this protease might be a plasminogen activator (Berstad & Briseid 1982; Johansen & Briseid 1983). Factor XII in the plasma preparation was activated to unfragmented factor XIIa by adsorption to kaolin, and assayed as prekallikrein activator (PKA). The extent of activation of factor XII was only insignificantly influenced by the 1 + 1 (v/v) dilution of the plasma preparation with a suspension of kaolin. When, however, the preparation was diluted greater than 1 + 5 (v/v) before incubation with the suspension, a stoichiometric HMrK concentration-effect curve could be established, allowing the assay of cofactor-active HMrK. Assays of HMrK in plasma preparations from healthy men and women demonstrated an average lower level of cofactor-active HMrK in the preparations from women. It is suggested that benzamidine is not capable of providing a complete protection of HMrK during the procedure in all plasma samples.","PeriodicalId":6972,"journal":{"name":"Acta pharmacologica et toxicologica","volume":"53 4","pages":"344-52"},"PeriodicalIF":0.0,"publicationDate":"1983-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1111/j.1600-0773.1983.tb03433.x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"17740600","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

Increased cytochrome P-450 independent drug metabolism and mutagen activation in rat liver by octachlorostyrene. 八氯苯乙烯增加大鼠肝脏细胞色素P-450独立药物代谢和诱变原活化。

Acta pharmacologica et toxicologica Pub Date : 1983-10-01 DOI: 10.1111/j.1600-0773.1983.tb03430.x

J A Holme, E Dybing

引用次数: 7

In vitro metabolism of propoxyphene in rat liver: reaction of a carbinol metabolite with acetaldehyde. 丙氧苯在大鼠肝脏的体外代谢:甲醇代谢物与乙醛的反应。

Acta pharmacologica et toxicologica Pub Date : 1983-10-01 DOI: 10.1111/j.1600-0773.1983.tb03421.x

I Hermansson, J Hermansson, N E Stjernström

引用次数: 4

Application of a primate model for tardive dyskinesia. 灵长类动物迟发性运动障碍模型的应用。

Acta pharmacologica et toxicologica Pub Date : 1983-02-01

S Bárány, J E Häggström, L M Gunne