Pub Date : 2000-10-01DOI: 10.1111/J.2042-7158.2000.TB00219.X
T. Murugesan, B. Rao, S. Sinha, S. Biswas, M. Pal, B. P. Saha
The hypoglycaemic and anti-hyperglycaemic potential of a methanolic extract of Jussiaea suffruticosa Linn. (family-Onagraceae) was evaluated in normal and alloxan-diabetic rats. In normal rats, the methanolic extract of J. suffruticosa Linn. (200 and 400 mg kg−1) exhibited significant hypoglycaemic activity (P < 0.05) within 3 h after oral administration. The plasma glucose concentration was 89.83±6 mg/100 mL (control 115.5±3.6 mg/100 mL) at 3h and 78.16±5.7 mg/100 mL (control 113.2±4.2 mg/100 mL) at 4.5 h after oral administration of 400 mg kg−1 of the methanolic extract. The effect was prolonged up to 24 h and the plasma glucose concentration fell to 75.66±5.5 mg/100 mL (control 112.16±3.7 mg/100 mL). The effect was dose-dependent. In alloxan-diabetic rats, the methanolic extract (400 mg kg−1) showed a significant anti-hyperglycaemic effect (P < 0.05) from 1.5 h after oral administration. This effect was prolonged up to 24 h and the plasma glucose concentration fell to 173.66±6 mg/100 mL (control 296.67±4.9 mg/100 mL) compared with 166.83±6.7 after oral administration of 10 mg kg−1 glibenclamide (standard). The results indicate that the methanolic extract of whole plants of J. suffruticosa Linn. has potent hypoglycaemic potential in normoglycaemic rats and alloxan-diabetic rats.
{"title":"Anti-diabetic Activity of Jussiaea suffruticosa Extract in Rats","authors":"T. Murugesan, B. Rao, S. Sinha, S. Biswas, M. Pal, B. P. Saha","doi":"10.1111/J.2042-7158.2000.TB00219.X","DOIUrl":"https://doi.org/10.1111/J.2042-7158.2000.TB00219.X","url":null,"abstract":"The hypoglycaemic and anti-hyperglycaemic potential of a methanolic extract of Jussiaea suffruticosa Linn. (family-Onagraceae) was evaluated in normal and alloxan-diabetic rats. \u0000 \u0000 \u0000 \u0000In normal rats, the methanolic extract of J. suffruticosa Linn. (200 and 400 mg kg−1) exhibited significant hypoglycaemic activity (P < 0.05) within 3 h after oral administration. The plasma glucose concentration was 89.83±6 mg/100 mL (control 115.5±3.6 mg/100 mL) at 3h and 78.16±5.7 mg/100 mL (control 113.2±4.2 mg/100 mL) at 4.5 h after oral administration of 400 mg kg−1 of the methanolic extract. The effect was prolonged up to 24 h and the plasma glucose concentration fell to 75.66±5.5 mg/100 mL (control 112.16±3.7 mg/100 mL). The effect was dose-dependent. In alloxan-diabetic rats, the methanolic extract (400 mg kg−1) showed a significant anti-hyperglycaemic effect (P < 0.05) from 1.5 h after oral administration. This effect was prolonged up to 24 h and the plasma glucose concentration fell to 173.66±6 mg/100 mL (control 296.67±4.9 mg/100 mL) compared with 166.83±6.7 after oral administration of 10 mg kg−1 glibenclamide (standard). \u0000 \u0000 \u0000 \u0000The results indicate that the methanolic extract of whole plants of J. suffruticosa Linn. has potent hypoglycaemic potential in normoglycaemic rats and alloxan-diabetic rats.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79117582","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 : 2000-10-01DOI: 10.1211/146080800128735539
P. O. Osadebe, P. Akah, C. O. Okafor, L. Natova
Six new ester derivatives of γ-(4-substituted piperazinyl)-α-phenyl propanol were prepared by esterification of the γ-piperazinyl propanols. The derivatives were methyl, ethyl, phenyl and benzyl esters, and they were obtained in good yields using a solid-liquid phase transfer catalysed esterification method. The nitrogen content of the new derivatives was also determined. Studies using isolated guineapig ileum showed that the derivatives possessed varying degrees of antispasmodic activity. Of the compounds evaluated, the ethyl ester of γ-(4-benzyl piperazin-1-yl)-α-phenyl propanol showed the greatest antispasmodic activity.
{"title":"Synthesis of Some Unsymmetrical Ester Derivatives of γ-(4-Substituted piperazin-1-yl)-α-phenyl propanols with Antispasmodic Activity","authors":"P. O. Osadebe, P. Akah, C. O. Okafor, L. Natova","doi":"10.1211/146080800128735539","DOIUrl":"https://doi.org/10.1211/146080800128735539","url":null,"abstract":"Six new ester derivatives of γ-(4-substituted piperazinyl)-α-phenyl propanol were prepared by esterification of the γ-piperazinyl propanols. \u0000 \u0000 \u0000 \u0000The derivatives were methyl, ethyl, phenyl and benzyl esters, and they were obtained in good yields using a solid-liquid phase transfer catalysed esterification method. The nitrogen content of the new derivatives was also determined. Studies using isolated guineapig ileum showed that the derivatives possessed varying degrees of antispasmodic activity. \u0000 \u0000 \u0000 \u0000Of the compounds evaluated, the ethyl ester of γ-(4-benzyl piperazin-1-yl)-α-phenyl propanol showed the greatest antispasmodic activity.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87556518","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 : 2000-10-01DOI: 10.1211/146080800128735520
J. Dhuley, S. Naik
γ-Glutamyl transpeptidase (γ-GTP) is known to play a vital role in the turnover of glutathione and protein synthesis. Hence, it is presumed that changes in the activity of γ-GTP in inflamed tissue itself might occur as both catabolic and anabolic processes are activated simultaneously in inflammation. The aim of this study was to determine γ-GTP activity in oedematous and granulomatous tissues in carrageenin-induced hind-paw oedema and cotton-pellet granuloma, respectively, in rats. In the time course study, maximum γ-GTP activity was observed in oedematous tissue at 4h after carrageenin injection and in granulomatous tissue on Day 7 after cotton-pellet implantation. Treatment with 6-MFA significantly inhibited the increase in γ-GTP activity in both oedematous and granulomatous tissues. The results suggest that the measurement of γ-GTP activity in inflammation may serve as a sensitive biochemical marker for evaluation of the in-vivo anti-inflammatory activity of drugs.
{"title":"Increased γ‐Glutamyl Transpeptidase Activity During Inflammation and its Inhibition by 6‐MFA, a Metabolite Obtained from Aspergillus ochraceus","authors":"J. Dhuley, S. Naik","doi":"10.1211/146080800128735520","DOIUrl":"https://doi.org/10.1211/146080800128735520","url":null,"abstract":"γ-Glutamyl transpeptidase (γ-GTP) is known to play a vital role in the turnover of glutathione and protein synthesis. Hence, it is presumed that changes in the activity of γ-GTP in inflamed tissue itself might occur as both catabolic and anabolic processes are activated simultaneously in inflammation. The aim of this study was to determine γ-GTP activity in oedematous and granulomatous tissues in carrageenin-induced hind-paw oedema and cotton-pellet granuloma, respectively, in rats. \u0000 \u0000 \u0000 \u0000In the time course study, maximum γ-GTP activity was observed in oedematous tissue at 4h after carrageenin injection and in granulomatous tissue on Day 7 after cotton-pellet implantation. Treatment with 6-MFA significantly inhibited the increase in γ-GTP activity in both oedematous and granulomatous tissues. \u0000 \u0000 \u0000 \u0000The results suggest that the measurement of γ-GTP activity in inflammation may serve as a sensitive biochemical marker for evaluation of the in-vivo anti-inflammatory activity of drugs.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74402670","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 : 2000-10-01DOI: 10.1211/146080800128735511
S. Mustafa
The aim of this study was to determine the mechanism responsible for the cyclopiazonic acid (CPA)-induced contraction of tracheal smooth muscle. CPA, an inhibitor of Ca2+-ATPase, induced a slowly developing contraction of ovine tracheal strips but had no effect on bronchiolar ring segments. CPA-induced contractions in tracheal strips were abolished in Ca2+-free Krebs solution containing 2 mM EGTA, and were significantly reduced in the presence of verapamil. Influx of 45Ca2+ into the tracheal strips was significantly increased in the presence of CPA. The results suggest that CPA induces contractions of ovine tracheal strips by promoting influx of extracellular Ca2+ through L-type voltage-dependent Ca2+ channels.
本研究的目的是确定环吡唑酸(CPA)诱导气管平滑肌收缩的机制。CPA是一种Ca2+- atp酶抑制剂，可诱导绵羊气管条缓慢收缩，但对细支气管环段无影响。在含有2 mM EGTA的无Ca2+ Krebs溶液中，cpa诱导的气管条收缩被消除，在维拉帕米的存在下，收缩明显减少。在CPA存在的情况下，45Ca2+流入气管条的量显著增加。结果表明，CPA通过l型电压依赖性Ca2+通道促进细胞外Ca2+的内流，从而诱导羊气管条收缩。
{"title":"Cyclopiazonic Acid Induces Contractions in Ovine Tracheal Smooth Muscle","authors":"S. Mustafa","doi":"10.1211/146080800128735511","DOIUrl":"https://doi.org/10.1211/146080800128735511","url":null,"abstract":"The aim of this study was to determine the mechanism responsible for the cyclopiazonic acid (CPA)-induced contraction of tracheal smooth muscle. \u0000 \u0000 \u0000 \u0000CPA, an inhibitor of Ca2+-ATPase, induced a slowly developing contraction of ovine tracheal strips but had no effect on bronchiolar ring segments. CPA-induced contractions in tracheal strips were abolished in Ca2+-free Krebs solution containing 2 mM EGTA, and were significantly reduced in the presence of verapamil. Influx of 45Ca2+ into the tracheal strips was significantly increased in the presence of CPA. \u0000 \u0000 \u0000 \u0000The results suggest that CPA induces contractions of ovine tracheal strips by promoting influx of extracellular Ca2+ through L-type voltage-dependent Ca2+ channels.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74508482","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 : 2000-10-01DOI: 10.1211/146080800128735476
M. Gohel, L. Patel
A co-grinding method was used to improve the dissolution characteristics of nimesulide, a poorly water-soluble non-steroidal anti-inflammatory drug. Nimesulide solubility was studied to determine the solubilization process using different concentrations of Tween 80 at different pH values. At a 10% Tween 80 concentration, a large proportion (> 90%) of drug was entrapped in micelles when the pH of buffer solution was greater than pKa of nimesulide. A 32 factorial design was adopted using the concentration of Tween 80 and sodium lauryl sulphate as independent variables. Improved drug dissolution was obtained when the drug was mixed first with aqueous surfactant solution and later blended with adjuvant such as lactose and microcrystalline cellulose. Sodium lauryl sulphate was more effective in increasing the drug dissolution compared with Tween 80. The use of a blend of Tween 80 and sodium lauryl sulphate is justified since the interaction term (Tween 80 x sodium lauryl sulphate) for percentage drug release in 45 and 120 min was not significant. Contour plots were obtained for the angle of repose and percentage drug release in 30, 45 and 120 min. The study revealed that optimum level of surfactants should be used. The granule flow was adversely affected and no further improvement of drug dissolution was observed when the surfactants were used at high levels. The improved drug dissolution may be attributed to improved wetting and micellization due to presence of surfactants or hydrophilic adjuvant. More than two-fold increase in the drug dissolution was obtained by the selected batches.
{"title":"Improvement of Nimesulide Dissolution by a Co‐grinding Method Using Surfactants","authors":"M. Gohel, L. Patel","doi":"10.1211/146080800128735476","DOIUrl":"https://doi.org/10.1211/146080800128735476","url":null,"abstract":"A co-grinding method was used to improve the dissolution characteristics of nimesulide, a poorly water-soluble non-steroidal anti-inflammatory drug. Nimesulide solubility was studied to determine the solubilization process using different concentrations of Tween 80 at different pH values. \u0000 \u0000 \u0000 \u0000At a 10% Tween 80 concentration, a large proportion (> 90%) of drug was entrapped in micelles when the pH of buffer solution was greater than pKa of nimesulide. A 32 factorial design was adopted using the concentration of Tween 80 and sodium lauryl sulphate as independent variables. Improved drug dissolution was obtained when the drug was mixed first with aqueous surfactant solution and later blended with adjuvant such as lactose and microcrystalline cellulose. Sodium lauryl sulphate was more effective in increasing the drug dissolution compared with Tween 80. The use of a blend of Tween 80 and sodium lauryl sulphate is justified since the interaction term (Tween 80 x sodium lauryl sulphate) for percentage drug release in 45 and 120 min was not significant. Contour plots were obtained for the angle of repose and percentage drug release in 30, 45 and 120 min. \u0000 \u0000 \u0000 \u0000The study revealed that optimum level of surfactants should be used. The granule flow was adversely affected and no further improvement of drug dissolution was observed when the surfactants were used at high levels. The improved drug dissolution may be attributed to improved wetting and micellization due to presence of surfactants or hydrophilic adjuvant. More than two-fold increase in the drug dissolution was obtained by the selected batches.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88218033","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 : 2000-10-01DOI: 10.1211/146080800128735502
S. Sardari, G. Amin, A. Sekhon, R. Micetich, M. Daneshtalab
The constituents and antifungal activity of Diplotaenia damavandica, a rare native plant growing in Iran, were investigated. A methanolic extract of D. damavandica was obtained. The fractionation and isolation of the components was performed using column chromatography and HPLC. Bioassayguided isolation of the extract led to the purification of four coumarin compounds, angelicin, libanorin, psoralen and auraptene. The antifungal activity against Candida albicans, Cryptococcus neoformans and Cladosporium cucumerinum was tested. The cytotoxicity of the fractions against the human KB cell line was evaluated. We conclude that the main antifungal component of D. damavandica is an angular furanocoumarin. The antifungal activity and low cytotoxicity of angelicin make it a potentially useful target for further research.
{"title":"Antifungal Activity of Diplotaenia damavandica","authors":"S. Sardari, G. Amin, A. Sekhon, R. Micetich, M. Daneshtalab","doi":"10.1211/146080800128735502","DOIUrl":"https://doi.org/10.1211/146080800128735502","url":null,"abstract":"The constituents and antifungal activity of Diplotaenia damavandica, a rare native plant growing in Iran, were investigated. \u0000 \u0000 \u0000 \u0000A methanolic extract of D. damavandica was obtained. The fractionation and isolation of the components was performed using column chromatography and HPLC. Bioassayguided isolation of the extract led to the purification of four coumarin compounds, angelicin, libanorin, psoralen and auraptene. The antifungal activity against Candida albicans, Cryptococcus neoformans and Cladosporium cucumerinum was tested. The cytotoxicity of the fractions against the human KB cell line was evaluated. \u0000 \u0000 \u0000 \u0000We conclude that the main antifungal component of D. damavandica is an angular furanocoumarin. The antifungal activity and low cytotoxicity of angelicin make it a potentially useful target for further research.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79277095","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 : 2000-10-01DOI: 10.1211/146080800128735494
F. Callejón, J. A. Duran, J. A. Abadín, A. Sánchez
The aim of this study was to demonstrate the sealing of a prototype stainless steel dialysis chamber and the reproducibility of the results after using the chamber to measure the free plasma fraction of cyclosporin. The chamber comprised two compartments (A and B), in each of which was a hemisphere of approximately 1-mL capacity. To demonstrate sealing, equilibrium dialysis was carried out simultaneously in 10 chambers, but in which the semipermeable membrane separating the two compartments was substituted by an impermeable membrane. Chamber sealing was checked by the absence of liquid in the compartment B at the end of dialysis. To test reproducibility, equilibrium dialysis was carried out in 10 chambers containing cyclosporin. The mean value for the free plasma fraction of cyclosporin was 0.65%, giving a coefficient of variation within the acceptable limit of error. The use of this stainless steel chamber is recommended when large numbers of dialyses of cyclosporin must be carried out frequently.
{"title":"Equilibrium Dialysis in a Stainless Steel Chamber, Measurement of the Free Plasma Fraction of Cyclosporin","authors":"F. Callejón, J. A. Duran, J. A. Abadín, A. Sánchez","doi":"10.1211/146080800128735494","DOIUrl":"https://doi.org/10.1211/146080800128735494","url":null,"abstract":"The aim of this study was to demonstrate the sealing of a prototype stainless steel dialysis chamber and the reproducibility of the results after using the chamber to measure the free plasma fraction of cyclosporin. \u0000 \u0000 \u0000 \u0000The chamber comprised two compartments (A and B), in each of which was a hemisphere of approximately 1-mL capacity. To demonstrate sealing, equilibrium dialysis was carried out simultaneously in 10 chambers, but in which the semipermeable membrane separating the two compartments was substituted by an impermeable membrane. Chamber sealing was checked by the absence of liquid in the compartment B at the end of dialysis. To test reproducibility, equilibrium dialysis was carried out in 10 chambers containing cyclosporin. The mean value for the free plasma fraction of cyclosporin was 0.65%, giving a coefficient of variation within the acceptable limit of error. \u0000 \u0000 \u0000 \u0000The use of this stainless steel chamber is recommended when large numbers of dialyses of cyclosporin must be carried out frequently.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84045560","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 : 2000-10-01DOI: 10.1211/146080800128735485
P. Dickinson, P. Seville, G. Taylor
The aim of this study was to synthesize an ester with low lipophilicity, and to use this ester to further investigate pre-absorptive pulmonary first-pass metabolism. Hexanoic acid phenethyl ester was synthesized by reacting 2-phenylethanol with hexanoyl chloride. Pre-absorptive first-pass metabolism was assessed by comparing the areas under the blood concentration-time curves after intra-arterial administration of the hexanoic acid phenethyl ester with those after intratracheal instillation. Hexanoic acid phenethyl ester experienced extensive first-pass metabolism (53% of the absorbed dose) before or during absorption. This and earlier data suggests that the extent of this first-pass extraction is dependent on the physicochemical properties of the ester and in particular whether a compound experiences diffusion-limited absorption. Pre-absorptive pulmonary first-pass metabolism of compounds whose absorption is diffusion-rate limited may be extensive even when pulmonary enzyme expression is low. This has consequences for the systemic delivery of drugs and in particular esters via the lungs.
{"title":"Further Evidence of Extensive Pulmonary First‐pass Ester Hydrolysis after Airways Administration in Rats","authors":"P. Dickinson, P. Seville, G. Taylor","doi":"10.1211/146080800128735485","DOIUrl":"https://doi.org/10.1211/146080800128735485","url":null,"abstract":"The aim of this study was to synthesize an ester with low lipophilicity, and to use this ester to further investigate pre-absorptive pulmonary first-pass metabolism. \u0000 \u0000 \u0000 \u0000Hexanoic acid phenethyl ester was synthesized by reacting 2-phenylethanol with hexanoyl chloride. Pre-absorptive first-pass metabolism was assessed by comparing the areas under the blood concentration-time curves after intra-arterial administration of the hexanoic acid phenethyl ester with those after intratracheal instillation. Hexanoic acid phenethyl ester experienced extensive first-pass metabolism (53% of the absorbed dose) before or during absorption. This and earlier data suggests that the extent of this first-pass extraction is dependent on the physicochemical properties of the ester and in particular whether a compound experiences diffusion-limited absorption. \u0000 \u0000 \u0000 \u0000Pre-absorptive pulmonary first-pass metabolism of compounds whose absorption is diffusion-rate limited may be extensive even when pulmonary enzyme expression is low. This has consequences for the systemic delivery of drugs and in particular esters via the lungs.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2000-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84609021","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: 10.1211/146080800128736268
Yoshio Tanaka Makoto Kamibayashi, F. Yamaki, M. Saitoh, T. Nakazawa, Hikaru Tanaka, K. Noguchi, K. Hashimoto, K. Shigenobu
HNS-32 (N1N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1-carbox-amidine) (CAS 186086-10-2) is a newly synthesized compound with an azulene structure within the molecule. The coronary relaxant action of HNS-32 was investigated pharmaco-mechanically on isolated pig coronary artery. The effects of HNS-32 were compared with diltiazem, a Ca2+-channel blocker. HNS-32 inhibited sustained contractions evoked by high KCl, prostaglandin F2α, a thromboxane A2 mimetic (U46619) and endothelin-1 in a concentration-dependent manner. The potency of HNS-32 to inhibit these contractions was 5- to 40-times lower than diltiazem. HNS-32 also diminished phasic contractions induced by acetylcholine, histamine and 5-hydroxytryptamine. Addition of excess Ca2+ counteracted HNS-32-induced inhibition of high KCl-induced contraction only by approximately 10% whereas it restored diltiazem-induced inhibition by about 50%. Suppression of the contractile response to a phorbol ester (phorbol 12,13-dibutyrate) by HNS-32 was approximately 40%. HNS-32 prevents coronary contractions produced by a wide variety of spasmogens. Although inhibitions of L-type Ca2+ channels and protein kinase C may be partly responsible for HNS-32 action, some direct action on the contractile systems seems to be involved in the coronary relaxation by HNS-32.
{"title":"Relaxant Action of Azulene‐1‐carboxamidine Derivative N1, N1‐dimethyl‐N2‐(2‐pyridylmethyl)‐5‐isopropyl‐3,8‐dimethylazulene‐1‐carboxamidine (HNS‐32) in Pig Coronary Artery","authors":"Yoshio Tanaka Makoto Kamibayashi, F. Yamaki, M. Saitoh, T. Nakazawa, Hikaru Tanaka, K. Noguchi, K. Hashimoto, K. Shigenobu","doi":"10.1211/146080800128736268","DOIUrl":"https://doi.org/10.1211/146080800128736268","url":null,"abstract":"HNS-32 (N1N1-dimethyl-N2-(2-pyridylmethyl)-5-isopropyl-3,8-dimethylazulene-1-carbox-amidine) (CAS 186086-10-2) is a newly synthesized compound with an azulene structure within the molecule. The coronary relaxant action of HNS-32 was investigated pharmaco-mechanically on isolated pig coronary artery. The effects of HNS-32 were compared with diltiazem, a Ca2+-channel blocker. \u0000 \u0000 \u0000 \u0000HNS-32 inhibited sustained contractions evoked by high KCl, prostaglandin F2α, a thromboxane A2 mimetic (U46619) and endothelin-1 in a concentration-dependent manner. The potency of HNS-32 to inhibit these contractions was 5- to 40-times lower than diltiazem. HNS-32 also diminished phasic contractions induced by acetylcholine, histamine and 5-hydroxytryptamine. Addition of excess Ca2+ counteracted HNS-32-induced inhibition of high KCl-induced contraction only by approximately 10% whereas it restored diltiazem-induced inhibition by about 50%. Suppression of the contractile response to a phorbol ester (phorbol 12,13-dibutyrate) by HNS-32 was approximately 40%. \u0000 \u0000 \u0000 \u0000HNS-32 prevents coronary contractions produced by a wide variety of spasmogens. Although inhibitions of L-type Ca2+ channels and protein kinase C may be partly responsible for HNS-32 action, some direct action on the contractile systems seems to be involved in the coronary relaxation by HNS-32.","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":"91535154","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: 10.1211/146080800128736277
Saranjit Singh, T. Mariappan, N. Sharda, Sanjeev Kumar, A. Chakraborti
The poor bioavailability of rifampicin from fixed-dose combinations containing isoniazid has been attributed to isoniazid-catalysed degradation under acid conditions in the stomach. The mechanism by which isoniazid enhances rifampicin degradation is not known. The aim of this study was to determine the role of isoniazid in rifampicin decomposition. Degradation studies were performed in 0.1 M HCl at 37°, in absence and presence of isoniazid. Both rifampicin and isoniazid were analysed. The degradation of rifampicin was increased approximately threefold in the presence of isoniazid. Isoniazid itself was degraded to a lesser extent amounting to one-fifth of the fall of rifampicin. HPLC studies revealed that decomposition of rifampicin in acidic conditions in the absence of isoniazid stopped at the formation of 3-formylrifamycin, while the reaction in the presence of isoniazid proceeded to form a hydrazone between 3-formylrifamycin and isoniazid. The existence of hydrazone was confirmed by its isolation on a preparative column and comparison with an authentic sample synthesized from reaction of 3-formylrifamycin with isoniazid. We suggest that once 3-formylrifamycin is formed, it interacts with isoniazid to form the hydrazone, through a fast second-order reaction. As hydrazones are unstable in acid conditions, 3-formylrifamycin and isoniazid are regenerated in a reversible manner through a slower first-order reaction. In this complex reaction process, rifampicin is further degraded, while isoniazid is recovered.
含有异烟肼的固定剂量组合中利福平的生物利用度较差归因于异烟肼在胃酸条件下催化降解。异烟肼促进利福平降解的机制尚不清楚。本研究的目的是确定异烟肼在利福平分解中的作用。在37°0.1 M HCl中，在不存在和不存在异烟肼的情况下进行降解研究。对利福平和异烟肼进行分析。在异烟肼的存在下，利福平的降解增加了大约三倍。异烟肼本身的降解程度较轻，仅为利福平的五分之一。HPLC研究发现，在没有异烟肼的酸性条件下，利福平的分解停止于生成3-甲酰基利福霉素，而在有异烟肼的情况下，反应继续进行，在3-甲酰基利福霉素和异烟肼之间形成腙。在制备柱上分离得到该化合物，并与异烟肼与3-甲酰基利福霉素反应合成的样品进行比较，证实了该化合物的存在。我们认为，一旦形成3-甲酰基利福霉素，它与异烟肼相互作用形成腙，通过一个快速的二级反应。由于腙在酸性条件下不稳定，3-甲酰基利福霉素和异烟肼通过较慢的一级反应以可逆的方式再生。在这个复杂的反应过程中，利福平被进一步降解，异烟肼被回收。
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