Pub Date : 2000-09-01DOI: 10.1211/146080800128736303
A. Sparatore, F. Sparatore
We have prepared and studied some new 2-methoxyphenylpiperazine derivatives as combined ligands for 5-hydroxytryptamine 5-HT1A and dopamine D3 receptor subtypes. The compounds displayed affinity for 5-HT1A and D3 receptors, which improved with the lengthening of the intermediate aliphatic chain. Conversely, binding to 5-HT2A, D2 and α1-receptor subtypes was affected in an irregular, and mainly negative, manner by the chain length. Benzotriazole derivatives with 4–5 methylenes exhibited good or excellent selectivity for 5-HT1A and D3 vs 5-HT2A, D2 and α1-receptors.
{"title":"2‐{4‐[ω‐[4‐(2‐Methoxyphenyl)‐1‐piperazinyl]alkoxy]phenyl}‐ 2H‐benzotriazoles and their N‐Oxides as Ligands for some 5‐Hydroxytryptamine, Dopamine and Adrenergic Receptor Subtypes","authors":"A. Sparatore, F. Sparatore","doi":"10.1211/146080800128736303","DOIUrl":"https://doi.org/10.1211/146080800128736303","url":null,"abstract":"We have prepared and studied some new 2-methoxyphenylpiperazine derivatives as combined ligands for 5-hydroxytryptamine 5-HT1A and dopamine D3 receptor subtypes. \u0000 \u0000 \u0000 \u0000The compounds displayed affinity for 5-HT1A and D3 receptors, which improved with the lengthening of the intermediate aliphatic chain. Conversely, binding to 5-HT2A, D2 and α1-receptor subtypes was affected in an irregular, and mainly negative, manner by the chain length. Benzotriazole derivatives with 4–5 methylenes exhibited good or excellent selectivity for 5-HT1A and D3 vs 5-HT2A, D2 and α1-receptors.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88580647","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}
Pub Date : 2000-09-01DOI: 10.1211/146080800128736286
M. Samini, M. Mohagheghi, F. Hasanzadeh, A. Dehpour
The anti-ulcer and gastroprotective effects of bromocriptine were studied in rats. Intraperitoneal administration of bromocriptine (2, 4 and 8 mg kg−1), a dopamine receptor agonist, which also acts on α-adrenoceptors, prevented indomethacin-induced gastric ulcer in rats dose-dependently. This protective effect was significantly blocked by the D1-receptor antagonist, SCH 23390 (1 mg kg−1, i.p.), the D2-receptor antagonist, sulpride (0.5 mg kg−1, i.p.) and the α2-receptor antagonist, yohimbine (5 mg kg−1, i.p.), suggesting that the effect of bromocriptine is mediated through dopamine receptors and α-adrenoceptors. We propose that the anti-ulcer effect of bromocriptine may be due to a decrease in acid secretion and gastric motility through activation of α2-adrenoceptors and dopamine D1 receptors.
研究溴隐亭对大鼠的抗溃疡和胃保护作用。腹腔注射溴隐亭(2、4和8 mg kg - 1)，一种多巴胺受体激动剂，也作用于α-肾上腺素受体，可呈剂量依赖性地预防吲哚美辛诱导的大鼠胃溃疡。这种保护作用被d1受体拮抗剂SCH 23390 (1 mg kg - 1, i.p)、d2受体拮抗剂sulpride (0.5 mg kg - 1, i.p)和α2受体拮抗剂育喜宾(5 mg kg - 1, i.p)显著阻断，表明溴隐亭的作用是通过多巴胺受体和α-肾上腺素受体介导的。我们认为溴隐亭的抗溃疡作用可能是通过激活α2-肾上腺素受体和多巴胺D1受体来减少胃酸分泌和胃运动。
{"title":"Anti‐ulcer Effect of Bromocriptine on Indomethacin‐induced Gastric Damage in Rats","authors":"M. Samini, M. Mohagheghi, F. Hasanzadeh, A. Dehpour","doi":"10.1211/146080800128736286","DOIUrl":"https://doi.org/10.1211/146080800128736286","url":null,"abstract":"The anti-ulcer and gastroprotective effects of bromocriptine were studied in rats. Intraperitoneal administration of bromocriptine (2, 4 and 8 mg kg−1), a dopamine receptor agonist, which also acts on α-adrenoceptors, prevented indomethacin-induced gastric ulcer in rats dose-dependently. This protective effect was significantly blocked by the D1-receptor antagonist, SCH 23390 (1 mg kg−1, i.p.), the D2-receptor antagonist, sulpride (0.5 mg kg−1, i.p.) and the α2-receptor antagonist, yohimbine (5 mg kg−1, i.p.), suggesting that the effect of bromocriptine is mediated through dopamine receptors and α-adrenoceptors. \u0000 \u0000 \u0000 \u0000We propose that the anti-ulcer effect of bromocriptine may be due to a decrease in acid secretion and gastric motility through activation of α2-adrenoceptors and dopamine D1 receptors.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85017835","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}
Pub Date : 2000-09-01DOI: 10.1211/146080800128736259
P. Coudert, C. Rubat, F. Rohet, F. Léal, J. Fialip, J. Couquelet
A new series of 4,6-diaryl pyridazin-3-ones substituted on the nitrogen atom in the 2-position have been prepared and evaluated for their analgesic activity in the phenylbenzo-quinone-induced abdominal constriction test. Most of the eighteen compounds displayed significant antinociceptive effects with ED50 ranging from 22-2 to 76-7 mg kg−1, intraperitoneally. Pyridazinones 4f and 5f were among the most interesting derivatives with marked analgesic properties associated to weak neurosedative activities (ED50 = 83-3 and 247-2 mg kg−1, i.p., respectively). Further investigations provided support for the hypothesis that the antinociceptive action of 4f and 5f probably resulted from interactions with opioidergic, 5-hydroxytryptaminergic and noradrenergic pathways.
{"title":"Synthesis of New Pyridazinones Substituted by 4-Arylpiperazin-1-yl-carbonylalkyl Moieties and their Analgesic Properties in Mice","authors":"P. Coudert, C. Rubat, F. Rohet, F. Léal, J. Fialip, J. Couquelet","doi":"10.1211/146080800128736259","DOIUrl":"https://doi.org/10.1211/146080800128736259","url":null,"abstract":"A new series of 4,6-diaryl pyridazin-3-ones substituted on the nitrogen atom in the 2-position have been prepared and evaluated for their analgesic activity in the phenylbenzo-quinone-induced abdominal constriction test. \u0000 \u0000 \u0000 \u0000Most of the eighteen compounds displayed significant antinociceptive effects with ED50 ranging from 22-2 to 76-7 mg kg−1, intraperitoneally. Pyridazinones 4f and 5f were among the most interesting derivatives with marked analgesic properties associated to weak neurosedative activities (ED50 = 83-3 and 247-2 mg kg−1, i.p., respectively). \u0000 \u0000 \u0000 \u0000Further investigations provided support for the hypothesis that the antinociceptive action of 4f and 5f probably resulted from interactions with opioidergic, 5-hydroxytryptaminergic and noradrenergic pathways.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80253175","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}
Pub Date : 2000-09-01DOI: 10.1211/146080800128736295
R. Korolkiewicz, Z. Konstański, P. Rekowski, J. Ruczyński, A. Szyk, R. Szczepańska, Korolkiewicz Kz, J. Petrusewicz
Galanin (Gal) constricts rat gastric fundus by acting on receptors located in the cell membrane. We compared the role of intracellular Ca2+ release with extracellular Ca2+ influx in Gal-stimulated contraction of isolated gastric smooth muscle strips. We also tested if phospholipase C (PLC) or protein kinase C (PKC) participate in the signal transduction cascade. Concentration-contraction curves were constructed non-cumulatively in the presence of atropine, hexamethonium, guanethidine and tetrodotoxin. The half-maximum effective concentration (EC50) of Gal was 21.62nM and Hill's coefficient was 1.02. The effects of Gal were decreased by diltiazem, Ca2+-deficiency in the buffer, Ca2+ removal from the extracellular medium or quercetin. Depletion of intracellular Ca2+-stores, ryanodine and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester diminished the contractile effect of Gal concentration-dependently. Trifluoroperazine and phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitors, neomycin and U-73122, attenuated the gastric fundus response to Gal, whereas phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D (PLD) blockers, D609 and propranolol, were ineffective. The inhibitors of PKC or myosin light chain kinase, calphostin C, chelerythrine, ML-7 and ML-9, lowered the myogenic activity of Gal. Our data confirmed that the stimulation of Gal receptors in gastric fundus is coupled to Ca2+ influx through voltage-dependent channels and intracellular Ca2+ release from ryanodine- and inositol 1,4,5-triphosphate-sensitive stores. Enzymes such as PI-PLC and PKC, but not PC-PLC or PLD, play a role in the signal transduction cascade. Calmodulin and myosin light chain kinase lie downstream of the increases in intracellular Ca2+ concentration evoked by Gal.
{"title":"Mechanisms of Galanin-induced Contraction of Isolated Rat Gastric Fundus Strips {","authors":"R. Korolkiewicz, Z. Konstański, P. Rekowski, J. Ruczyński, A. Szyk, R. Szczepańska, Korolkiewicz Kz, J. Petrusewicz","doi":"10.1211/146080800128736295","DOIUrl":"https://doi.org/10.1211/146080800128736295","url":null,"abstract":"Galanin (Gal) constricts rat gastric fundus by acting on receptors located in the cell membrane. We compared the role of intracellular Ca2+ release with extracellular Ca2+ influx in Gal-stimulated contraction of isolated gastric smooth muscle strips. We also tested if phospholipase C (PLC) or protein kinase C (PKC) participate in the signal transduction cascade. \u0000 \u0000 \u0000 \u0000Concentration-contraction curves were constructed non-cumulatively in the presence of atropine, hexamethonium, guanethidine and tetrodotoxin. The half-maximum effective concentration (EC50) of Gal was 21.62nM and Hill's coefficient was 1.02. The effects of Gal were decreased by diltiazem, Ca2+-deficiency in the buffer, Ca2+ removal from the extracellular medium or quercetin. Depletion of intracellular Ca2+-stores, ryanodine and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)-octyl ester diminished the contractile effect of Gal concentration-dependently. Trifluoroperazine and phosphatidylinositol-specific phospholipase C (PI-PLC) inhibitors, neomycin and U-73122, attenuated the gastric fundus response to Gal, whereas phosphatidylcholine-specific phospholipase C (PC-PLC) and phospholipase D (PLD) blockers, D609 and propranolol, were ineffective. The inhibitors of PKC or myosin light chain kinase, calphostin C, chelerythrine, ML-7 and ML-9, lowered the myogenic activity of Gal. \u0000 \u0000 \u0000 \u0000Our data confirmed that the stimulation of Gal receptors in gastric fundus is coupled to Ca2+ influx through voltage-dependent channels and intracellular Ca2+ release from ryanodine- and inositol 1,4,5-triphosphate-sensitive stores. Enzymes such as PI-PLC and PKC, but not PC-PLC or PLD, play a role in the signal transduction cascade. Calmodulin and myosin light chain kinase lie downstream of the increases in intracellular Ca2+ concentration evoked by Gal.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86911730","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}
Pub Date : 2000-09-01DOI: 10.1211/146080800128736312
H. Fujiwara, K. Matsunaga, H. Kumagai, M. Ishizuka, Y. Ohizumi
We isolated ophiobolin A from the f-7438 fungus strain. In the L1210 cell line, ophiobolin A (0-01-1 μM) showed cytotoxicity in a concentration-dependent manner. Morphological observations revealed that ophiobolin A (1 μM) induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. Moreover, in DNA gel electrophoretic experiments, a typical apoptotic DNA ladder pattern was observed after treatment with this compound. The flow cytometric experiment indicated that ophiobolin A (0.01-1 μM) caused a concentration-dependent apoptosis in close agreement with concentrations that induced cytotoxicity in L1210 cells. The results suggested that ophiobolin A caused the death of L1210 cells through the apoptotic process. Ophiobolin A may become a powerful pharmacological tool for studying the apoptotic mechanism.
{"title":"Ophiobolin A, a Novel Apoptosis‐inducing Agent from Fungus Strain f‐7438","authors":"H. Fujiwara, K. Matsunaga, H. Kumagai, M. Ishizuka, Y. Ohizumi","doi":"10.1211/146080800128736312","DOIUrl":"https://doi.org/10.1211/146080800128736312","url":null,"abstract":"We isolated ophiobolin A from the f-7438 fungus strain. \u0000 \u0000 \u0000 \u0000In the L1210 cell line, ophiobolin A (0-01-1 μM) showed cytotoxicity in a concentration-dependent manner. Morphological observations revealed that ophiobolin A (1 μM) induced shrinkage in cell soma and chromatin condensation, suggesting apoptotic cell death. Moreover, in DNA gel electrophoretic experiments, a typical apoptotic DNA ladder pattern was observed after treatment with this compound. The flow cytometric experiment indicated that ophiobolin A (0.01-1 μM) caused a concentration-dependent apoptosis in close agreement with concentrations that induced cytotoxicity in L1210 cells. \u0000 \u0000 \u0000 \u0000The results suggested that ophiobolin A caused the death of L1210 cells through the apoptotic process. Ophiobolin A may become a powerful pharmacological tool for studying the apoptotic mechanism.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78076127","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}
Pub Date : 2000-09-01DOI: 10.1211/146080800128736240
V. Cardile, M. Renis, B. Gentile, A. Panico
We have studied the in-vitro effects of liposomal formulations loaded with three oligopeptides (Tp3, Tp4, Tp5), synthetic analogues corresponding to the active site of thymopoietin, on human thymic epithelial cells. The activity of the peptides entrapped in multilamellar vesicles and in stable plurilamellar liposomal vesicles, with or without cholesterol and containing stearylamine or dipalmitoylphosphatidyl serine, as positive or negative charge-inducer, was tested. The tetrazolium salt assay was performed as a marker of cell growth. To study the response of thymic epithelial cell cultures to liposome addition-dependent stress, we investigated the changes in the level of heat shock proteins (HSPs70). The results indicated that in-vitro among the peptides tested only Tp4 increased thymic epithelial cell growth. These stimulating effects were improved further when the peptide was entrapped in neutral 1,2-dipalmitoyl-L-α-phosphatidylcholine/cholesterol liposomes. Tp4 was also effective in modulating HSP70 protective effects.
{"title":"Activity of Liposome‐entrapped Immunomodulator Oligopeptides on Human Epithelial Thymic Cells","authors":"V. Cardile, M. Renis, B. Gentile, A. Panico","doi":"10.1211/146080800128736240","DOIUrl":"https://doi.org/10.1211/146080800128736240","url":null,"abstract":"We have studied the in-vitro effects of liposomal formulations loaded with three oligopeptides (Tp3, Tp4, Tp5), synthetic analogues corresponding to the active site of thymopoietin, on human thymic epithelial cells. \u0000 \u0000 \u0000 \u0000The activity of the peptides entrapped in multilamellar vesicles and in stable plurilamellar liposomal vesicles, with or without cholesterol and containing stearylamine or dipalmitoylphosphatidyl serine, as positive or negative charge-inducer, was tested. The tetrazolium salt assay was performed as a marker of cell growth. To study the response of thymic epithelial cell cultures to liposome addition-dependent stress, we investigated the changes in the level of heat shock proteins (HSPs70). \u0000 \u0000 \u0000 \u0000The results indicated that in-vitro among the peptides tested only Tp4 increased thymic epithelial cell growth. These stimulating effects were improved further when the peptide was entrapped in neutral 1,2-dipalmitoyl-L-α-phosphatidylcholine/cholesterol liposomes. Tp4 was also effective in modulating HSP70 protective effects.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86403883","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}
Pub Date : 2000-08-01DOI: 10.1211/146080800128736222
K. Kusano, H. Naito, T. Aiuchi, S. Nakajo, K. Nakaya
We have shown previously that extracellular ATP and bradykinin can stimulate the release of mucin from cultured human pulmonary mucoepidermoid carcinoma cells (NCI-H292) (Kusano et al 1997). Using this same cell culture system, we studied the mechanism by which this ATP- and bradykinin-induced mucin release occurs. We found that the mucin secretory response to ATP was not significantly affected by extracellular Ca2+ depletion, but the response to bradykinin was significantly inhibited by Ca2+-free medium. ATP and bradykinin increased the concentration of free intracellular Ca2+ ([Ca2+]i); the ATP-stimulated response was not affected by extracellular Ca2+ depletion, the bradykinin-stimulated response was prevented in the absence of extracellular Ca2+. ATP and bradykinin enhanced the accumulation of inositol 1,4,5-triphosphate in NCI-H292 cells and pretreatment with pertussis toxin blocked the increase in mucin secretion induced by extracellular ATP or bradykinin. These results suggest that extracellular ATP and bradykinin stimulate mucin release from NCI-H292 cells by a signal transduction that seems to involve ATP- or bradykinin-activated receptors associated with phospholipase C via pertussis toxin-sensitive GTP-binding proteins. These findings may suggest a new direction of research into the regulation of airway mucin secretion.
我们之前已经证明，细胞外ATP和缓激肽可以刺激培养的人肺黏液表皮样癌细胞(NCI-H292)释放黏液蛋白(Kusano et al 1997)。使用相同的细胞培养系统，我们研究了ATP和缓激肽诱导的粘蛋白释放发生的机制。我们发现，黏蛋白分泌对ATP的反应不受细胞外Ca2+消耗的显著影响，但对缓激肽的反应被Ca2+ free培养基显著抑制。ATP和缓激素使胞内游离Ca2+ ([Ca2+]i)浓度升高;atp刺激的反应不受细胞外Ca2+消耗的影响，在细胞外Ca2+缺乏的情况下，缓激素刺激的反应被阻止。ATP和缓激肽增强了NCI-H292细胞中肌醇1,4,5-三磷酸的积累，百日咳毒素预处理可阻断细胞外ATP或缓激肽诱导的黏液分泌增加。这些结果表明，细胞外ATP和缓激肽通过信号转导刺激NCI-H292细胞释放粘蛋白，该信号转导似乎涉及ATP或缓激肽激活的与磷脂酶C相关的受体，通过百日咳毒素敏感的gtp结合蛋白。这些发现可能为气道粘蛋白分泌调控的研究提供了新的方向。
{"title":"Mechanism of calcium on ATP-and bradykinin-induced mucin secretion from human pulmonary mucoepidermoid carcinoma cell lines","authors":"K. Kusano, H. Naito, T. Aiuchi, S. Nakajo, K. Nakaya","doi":"10.1211/146080800128736222","DOIUrl":"https://doi.org/10.1211/146080800128736222","url":null,"abstract":"We have shown previously that extracellular ATP and bradykinin can stimulate the release of mucin from cultured human pulmonary mucoepidermoid carcinoma cells (NCI-H292) (Kusano et al 1997). Using this same cell culture system, we studied the mechanism by which this ATP- and bradykinin-induced mucin release occurs. \u0000 \u0000 \u0000 \u0000We found that the mucin secretory response to ATP was not significantly affected by extracellular Ca2+ depletion, but the response to bradykinin was significantly inhibited by Ca2+-free medium. ATP and bradykinin increased the concentration of free intracellular Ca2+ ([Ca2+]i); the ATP-stimulated response was not affected by extracellular Ca2+ depletion, the bradykinin-stimulated response was prevented in the absence of extracellular Ca2+. ATP and bradykinin enhanced the accumulation of inositol 1,4,5-triphosphate in NCI-H292 cells and pretreatment with pertussis toxin blocked the increase in mucin secretion induced by extracellular ATP or bradykinin. \u0000 \u0000 \u0000 \u0000These results suggest that extracellular ATP and bradykinin stimulate mucin release from NCI-H292 cells by a signal transduction that seems to involve ATP- or bradykinin-activated receptors associated with phospholipase C via pertussis toxin-sensitive GTP-binding proteins. These findings may suggest a new direction of research into the regulation of airway mucin secretion.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76781602","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}
Pub Date : 2000-08-01DOI: 10.1211/146080800128736213
H. Tajerzadeh, M. Rouini, M. Afshar
This study was performed to determine the effect of food on the pharmacokinetic parameters of ranitidine. In a randomized crossover study, four healthy volunteers received a 150-mg tablet of ranitidine in the fasted state and, two weeks later, after eating a standard breakfast. Blood samples were taken frequently and analysed by reversed-phase HPLC. With all volunteers secondary peaks were present in the drug concentration-time profiles after administration in the fasted state; these were not present after administration of the drug in the fed state. Differences between AUC(0-∞) (the area under the plot of concentration against time) and between tmax (the time of maximum concentration) in the fasted and fed states were not significant, but Cmax (maximum concentration, fed state) and C1max (the first peak of concentration in the concentration-time profile, fasted state) were significantly different. This difference resulted in short tmax and relatively high Cmax in the presence of food.
{"title":"The Benefit of Administering Ranitidine with Food","authors":"H. Tajerzadeh, M. Rouini, M. Afshar","doi":"10.1211/146080800128736213","DOIUrl":"https://doi.org/10.1211/146080800128736213","url":null,"abstract":"This study was performed to determine the effect of food on the pharmacokinetic parameters of ranitidine. In a randomized crossover study, four healthy volunteers received a 150-mg tablet of ranitidine in the fasted state and, two weeks later, after eating a standard breakfast. Blood samples were taken frequently and analysed by reversed-phase HPLC. \u0000 \u0000 \u0000 \u0000With all volunteers secondary peaks were present in the drug concentration-time profiles after administration in the fasted state; these were not present after administration of the drug in the fed state. Differences between AUC(0-∞) (the area under the plot of concentration against time) and between tmax (the time of maximum concentration) in the fasted and fed states were not significant, but Cmax (maximum concentration, fed state) and C1max (the first peak of concentration in the concentration-time profile, fasted state) were significantly different. This difference resulted in short tmax and relatively high Cmax in the presence of food.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82912324","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}
Pub Date : 2000-08-01DOI: 10.1211/146080800128736178
A. Zarghi, S. Dadashzadeh, A. Ebrahimian
A rapid, simple and sensitive reversed-phase HPLC method has been developed for quantification of diltiazem in plasma. The assay enables the measurement of diltiazem for therapeutic drug monitoring with a minimum detectable limit of 2 ng mL−1. The method involves simple, one-step solvent extraction of the drug with 50:50 (v/v) n-hexane-ether then HPLC on an analytical C18 column with 35:35:30:0.05 ammonium chloride (0.04M)-methanol-acetonitrile-triethylamine, adjusted to pH6.3, as isocratic mobile phase. Diltiazem was monitored by ultra-violet detection at 237 nm. The calibration curve was linear over the concentration range 8–200 ng mL−1 and average recovery was 90±5.3% over the concentration range 50–300 ng mL−1. The coefficients of variation for inter-day and intra-day assay were within the range of clinical usefulness.
建立了一种快速、简便、灵敏的血浆中地尔硫卓的反相高效液相色谱测定方法。该分析能够测量地尔硫卓用于治疗药物监测，最低检测限为2 ng mL−1。方法以50:50 (v/v)正己烷-醚为溶剂，一步提取，以35:35:30:0.05氯化铵(0.04M)-甲醇-乙腈-三乙胺为等容流动相，以C18色谱柱为高效液相色谱柱。采用237 nm紫外检测法监测地尔硫卓。在浓度8 ~ 200 ng mL−1范围内，曲线呈线性关系;在浓度50 ~ 300 ng mL−1范围内，平均回收率为90±5.3%。日间和日间测定的变异系数均在临床有用的范围内。
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Pub Date : 2000-08-01DOI: 10.1211/146080800128736231
V. Sujatha, P. Sachdanandam
Plants are rich sources of natural products used in the treatment of diseases. Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. Because of its wide therapeutic utility, Semecarpus anacardium nut milk extract (Serankottai nei) has been tested against experimental mammary carcinoma in rats. Because the activity of tumour marker enzymes is proportional to the extent of malignancy, changes in the activity of these enzymes from the livers and kidneys of experimental rats were used as indices to assess the antineoplastic potency of the drug. A significant reduction in the activity of aspartate and alanine aminotransferases and a sharp increase in that of lactate dehydrogenase, γ-glutamyl transpeptidase, alkaline phosphatase and 5′-nucleotidase were observed in animals with mammary carcinoma. On administration of Semecarpus anacardium nut extract the activity of these enzymes returned almost to normal control levels. No adverse symptoms or significant changes were observed in drug control rats when compared with normal control rats.
{"title":"Effect of Semecarpus anacardium Linn. Nut Extract on Experimental Mammary Carcinoma in Sprague‐Dawley Rats with Reference to Tumour Marker Enzymes","authors":"V. Sujatha, P. Sachdanandam","doi":"10.1211/146080800128736231","DOIUrl":"https://doi.org/10.1211/146080800128736231","url":null,"abstract":"Plants are rich sources of natural products used in the treatment of diseases. Semecarpus anacardium Linn. of the family Anacardiaceae has many applications in the Ayurvedic and Siddha systems of medicine. Because of its wide therapeutic utility, Semecarpus anacardium nut milk extract (Serankottai nei) has been tested against experimental mammary carcinoma in rats. \u0000 \u0000 \u0000 \u0000Because the activity of tumour marker enzymes is proportional to the extent of malignancy, changes in the activity of these enzymes from the livers and kidneys of experimental rats were used as indices to assess the antineoplastic potency of the drug. A significant reduction in the activity of aspartate and alanine aminotransferases and a sharp increase in that of lactate dehydrogenase, γ-glutamyl transpeptidase, alkaline phosphatase and 5′-nucleotidase were observed in animals with mammary carcinoma. \u0000 \u0000 \u0000 \u0000On administration of Semecarpus anacardium nut extract the activity of these enzymes returned almost to normal control levels. No adverse symptoms or significant changes were observed in drug control rats when compared with normal control rats.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91549783","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}
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