Pub Date : 2000-02-01DOI: 10.1211/146080800128735700
R. Ouedraogo, J. Fontaine, M. Antoine, B. Pirotte, P. Lebrun
New 3-alkylaminopyridothiadiazine dioxides have been synthesized and characterized in a search for more efficient and selective KATP-channel activators. The new compounds induced concentration-dependent relaxation of vascular (aorta) and gastrointestinal (ileum) smooth muscle. The pharmacological profiles of the new compounds were different from those of diazoxide or pinacidil but similar to that of verapamil. The results suggest that the myorelaxant properties of the new compounds depend on their capacity to reduce calcium inflow into smooth muscle cells.
{"title":"Effects of 3-alkylamino-7-chloro-4H-pyrido[2,3-e]-1,2,4-thiadiazine 1,1-dioxides on smooth muscle contractile activity","authors":"R. Ouedraogo, J. Fontaine, M. Antoine, B. Pirotte, P. Lebrun","doi":"10.1211/146080800128735700","DOIUrl":"https://doi.org/10.1211/146080800128735700","url":null,"abstract":"New 3-alkylaminopyridothiadiazine dioxides have been synthesized and characterized in a search for more efficient and selective KATP-channel activators. \u0000 \u0000 \u0000 \u0000The new compounds induced concentration-dependent relaxation of vascular (aorta) and gastrointestinal (ileum) smooth muscle. The pharmacological profiles of the new compounds were different from those of diazoxide or pinacidil but similar to that of verapamil. \u0000 \u0000 \u0000 \u0000The results suggest that the myorelaxant properties of the new compounds depend on their capacity to reduce calcium inflow into smooth muscle cells.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"183 1","pages":"97-100"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80437065","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 : 2000-02-01DOI: 10.1211/146080800128735656
A. Hinschberger, Alain-Claude Gillard, F. Dauphin, S. Rault
Synthesis of new analogues of DR 4004, derived from 1,2,3,4,5,6,-hexahydrobenzo-[H][1,6]naphthyridin-5-ones is described. Their central pharmacological effects on the 5-HT7 receptor have been studied in-vitro.
{"title":"1,2,3,4,5,6‐Hexahydrobenzo[h][1,6]naphthyridin‐5‐ones: 5‐HT7 Receptor Affinity","authors":"A. Hinschberger, Alain-Claude Gillard, F. Dauphin, S. Rault","doi":"10.1211/146080800128735656","DOIUrl":"https://doi.org/10.1211/146080800128735656","url":null,"abstract":"Synthesis of new analogues of DR 4004, derived from 1,2,3,4,5,6,-hexahydrobenzo-[H][1,6]naphthyridin-5-ones is described. Their central pharmacological effects on the 5-HT7 receptor have been studied in-vitro.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"25 1","pages":"67-71"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81381521","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 : 2000-02-01DOI: 10.1211/096089296765556980
F. Somers, P. Tullio, S. Boverie, J. Dogné, X. Leval, M. Antoine, P. Lebrun, B. Pirotte
3-Alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides with nitro, amino or acetylamino groups in the 7-position have been synthesized in an attempt to discover new tissue-selective KATP-channel openers. The compounds were tested as putative pancreatic β-cells KATP-channel openers by measuring their inhibitory activity on the insulin releasing process. The influence of the substituent in the 7-position on the acidic character (pKa) and on biological activity is discussed. The nitrobenzene derivatives were biologically active, but less so than the un-derivatized parent pyridothiadiazine dioxides.
{"title":"Synthesis and biological effects of new 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides on insulin-secreting cells","authors":"F. Somers, P. Tullio, S. Boverie, J. Dogné, X. Leval, M. Antoine, P. Lebrun, B. Pirotte","doi":"10.1211/096089296765556980","DOIUrl":"https://doi.org/10.1211/096089296765556980","url":null,"abstract":"3-Alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides with nitro, amino or acetylamino groups in the 7-position have been synthesized in an attempt to discover new tissue-selective KATP-channel openers. \u0000 \u0000The compounds were tested as putative pancreatic β-cells KATP-channel openers by measuring their inhibitory activity on the insulin releasing process. The influence of the substituent in the 7-position on the acidic character (pKa) and on biological activity is discussed. \u0000 \u0000The nitrobenzene derivatives were biologically active, but less so than the un-derivatized parent pyridothiadiazine dioxides.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"10 1","pages":"89-95"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84473958","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 : 2000-02-01DOI: 10.1211/146080800128735665
C. Daveu, R. Bureau, S. Rault
A three-dimensional (3D) pharmacophore for 5-HT3 partial agonists has been developed, using the Catalyst program from a study of 3D structure-activity relationships. The 3D pharmacophore has three chemical features in common with 5-hydroxy-tryptamine (5-HT)—an aromatic ring, a basic centre and a hydrogen-bond-acceptor group. Comparison of 5-HT conformations observed in crystals, and of computed conformations, with the pharmacophore has enabled identification of a biologically active conformation of 5-HT for 5-HT3 receptors, and an extended conformation of 5-HT has been found to agree with the three-dimensional arrangement of the pharmacophoric elements. This conformation of 5-HT might be required for interaction with 5-HT3 receptors in binding sites.
{"title":"Relationship Between the 5‐HT3 Receptor Pharmacophore and the Conformations of 5‐Hydroxytryptamine","authors":"C. Daveu, R. Bureau, S. Rault","doi":"10.1211/146080800128735665","DOIUrl":"https://doi.org/10.1211/146080800128735665","url":null,"abstract":"A three-dimensional (3D) pharmacophore for 5-HT3 partial agonists has been developed, using the Catalyst program from a study of 3D structure-activity relationships. \u0000 \u0000 \u0000 \u0000The 3D pharmacophore has three chemical features in common with 5-hydroxy-tryptamine (5-HT)—an aromatic ring, a basic centre and a hydrogen-bond-acceptor group. Comparison of 5-HT conformations observed in crystals, and of computed conformations, with the pharmacophore has enabled identification of a biologically active conformation of 5-HT for 5-HT3 receptors, and an extended conformation of 5-HT has been found to agree with the three-dimensional arrangement of the pharmacophoric elements. This conformation of 5-HT might be required for interaction with 5-HT3 receptors in binding sites.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"92 1","pages":"73-76"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77464843","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 : 2000-02-01DOI: 10.1211/146080800128735674
J. Dogné, X. Leval, P. Neven, S. Rolin, J. Wouters, J. Delarge, B. Masereel
Because torasemide, a loop diuretic, dose-dependently relaxes canine coronary artery precontracted with thromboxane A2 (TxA2), a series of pyridine derivatives have been investigated with the aim of developing original TxA2 receptor antagonists. A binding test showed the affinity (IC50; the dose reducing binding by 50%) of one sulphonylurea derivative (BM 27) and two sulphonylcyanoguanidine derivatives (BM 114 and BM 115) for the TxA2 receptor of washed platelets from man were 161, 1. 75 and 0.54 μM, respectively. The IC50 of torasemide was only 2.69 μM. Their antagonism was confirmed by the capacity of the compounds to prevent the aggregation of platelets, from man, induced by arachidonic acid, the biological precursor of TxA2 (IC50: BM 114, 29.3 μM; BM 115, 12.0 μM; BM 27, 234 μM; torasemide, 350 μM; sulotroban, 12.3 μM). Similar results were obtained with the best compound BM 115 (IC50 11.5 μM) when U-46619, a stable TxA2 agonist, was used as the aggregating agent. This molecule can be regarded as a template for the design of novel non-carboxylic TxA2 receptor antagonists.
{"title":"Pharmacomodulation Studies of Torasemide Leading to Original Non‐carboxylic Thromboxane A2 Receptor Antagonists","authors":"J. Dogné, X. Leval, P. Neven, S. Rolin, J. Wouters, J. Delarge, B. Masereel","doi":"10.1211/146080800128735674","DOIUrl":"https://doi.org/10.1211/146080800128735674","url":null,"abstract":"Because torasemide, a loop diuretic, dose-dependently relaxes canine coronary artery precontracted with thromboxane A2 (TxA2), a series of pyridine derivatives have been investigated with the aim of developing original TxA2 receptor antagonists. \u0000 \u0000 \u0000 \u0000A binding test showed the affinity (IC50; the dose reducing binding by 50%) of one sulphonylurea derivative (BM 27) and two sulphonylcyanoguanidine derivatives (BM 114 and BM 115) for the TxA2 receptor of washed platelets from man were 161, 1. 75 and 0.54 μM, respectively. The IC50 of torasemide was only 2.69 μM. Their antagonism was confirmed by the capacity of the compounds to prevent the aggregation of platelets, from man, induced by arachidonic acid, the biological precursor of TxA2 (IC50: BM 114, 29.3 μM; BM 115, 12.0 μM; BM 27, 234 μM; torasemide, 350 μM; sulotroban, 12.3 μM). Similar results were obtained with the best compound BM 115 (IC50 11.5 μM) when U-46619, a stable TxA2 agonist, was used as the aggregating agent. \u0000 \u0000 \u0000 \u0000This molecule can be regarded as a template for the design of novel non-carboxylic TxA2 receptor antagonists.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"10 1","pages":"77-82"},"PeriodicalIF":0.0,"publicationDate":"2000-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78283401","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 : 2000-01-01DOI: 10.1211/146080800128735395
P. Barry, C. O’Callaghan
The aim of this study was to determine the delivery of two different drugs from spacer devices of different lengths and diameter. Spacer devices were prepared from lengths of plastic tubing of length 5, 10, 20, 50 and 100 cm, and diameter 30, 50 and 100 mm. Metered dose inhalers of sodium cromoglycate and budesonide were actuated into the spacers and drug output and particle size were measured using a glass multistage liquid impinger. To determine the effect of delay on the recovery of drug from the spacers, budesonide was actuated into spacers and output measured after a delay of 5, 10 or 20 s. For both drugs, increasing spacer length up to 20 cm increased drug recovery. There was no further increase or reduction with longer spacers. Increasing spacer diameter also increased drug recovery, although the increase was greater for sodium cromoglycate than budesonide. Budesonide delivery was greatest for spacers with a volume of 300 mL or greater, whereas maximum sodium cromoglycate delivery was from spacers with a volume of 1000 mL or greater. Drug half-life was also longer in larger spacers, being 6 s in a 10 cm length spacer (196 mL volume) and 15 s in a 20 cm length spacer (392 mL volume). The optimum spacer size was different for the two drugs. Sodium cromoglycate is best delivered from a larger spacer than budesonide. Conclusions from studies with one drug and spacer combination cannot be applied to another.
{"title":"The optimum length and width for a spacer device","authors":"P. Barry, C. O’Callaghan","doi":"10.1211/146080800128735395","DOIUrl":"https://doi.org/10.1211/146080800128735395","url":null,"abstract":"The aim of this study was to determine the delivery of two different drugs from spacer devices of different lengths and diameter. Spacer devices were prepared from lengths of plastic tubing of length 5, 10, 20, 50 and 100 cm, and diameter 30, 50 and 100 mm. Metered dose inhalers of sodium cromoglycate and budesonide were actuated into the spacers and drug output and particle size were measured using a glass multistage liquid impinger. To determine the effect of delay on the recovery of drug from the spacers, budesonide was actuated into spacers and output measured after a delay of 5, 10 or 20 s. For both drugs, increasing spacer length up to 20 cm increased drug recovery. There was no further increase or reduction with longer spacers. Increasing spacer diameter also increased drug recovery, although the increase was greater for sodium cromoglycate than budesonide. Budesonide delivery was greatest for spacers with a volume of 300 mL or greater, whereas maximum sodium cromoglycate delivery was from spacers with a volume of 1000 mL or greater. Drug half-life was also longer in larger spacers, being 6 s in a 10 cm length spacer (196 mL volume) and 15 s in a 20 cm length spacer (392 mL volume). The optimum spacer size was different for the two drugs. Sodium cromoglycate is best delivered from a larger spacer than budesonide. Conclusions from studies with one drug and spacer combination cannot be applied to another.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"1 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73723775","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 : 2000-01-01DOI: 10.1211/146080800128735430
A. Foroumadi, S. Tabatabai, G. Gitinezhad, M. Zarrindast, A. Shafiee
5-Aryl-1,3,4-thiadiazole derivatives were synthesized and tested for anticonvulsant activity using the pentylenetetrazole-induced lethal convulsion test. The results showed that 2-amino derivatives have anticon vulsant activity (LD50 > 500mg kg−1) and this effect was not mediated through benzodiazepine receptors. The fluoro electron-withdrawing substituent on the phenyl ring did not potentiate the activity of the compounds.
合成了5-芳基-1,3,4-噻二唑衍生物，并采用戊四唑致死性惊厥试验检测了其抗惊厥活性。结果表明，2-氨基衍生物具有抗兀蚁活性(LD50 > 500mg kg - 1)，且这种作用不通过苯二氮卓类受体介导。苯基环上的氟吸电子取代基没有增强化合物的活性。
{"title":"SYNTHESIS AND ANTICONVULSANT ACTIVITY OF 5-ARYL-1,3,4-THIADIAZOLE DERIVATIVES","authors":"A. Foroumadi, S. Tabatabai, G. Gitinezhad, M. Zarrindast, A. Shafiee","doi":"10.1211/146080800128735430","DOIUrl":"https://doi.org/10.1211/146080800128735430","url":null,"abstract":"5-Aryl-1,3,4-thiadiazole derivatives were synthesized and tested for anticonvulsant activity using the pentylenetetrazole-induced lethal convulsion test. The results showed that 2-amino derivatives have anticon vulsant activity (LD50 > 500mg kg−1) and this effect was not mediated through benzodiazepine receptors. The fluoro electron-withdrawing substituent on the phenyl ring did not potentiate the activity of the compounds.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"107 1","pages":"31-33"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72889453","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 : 2000-01-01DOI: 10.1211/146080800128735403
N. Sarisuta, M. Kumpugdee
The crystallinity of omeprazole in six film-forming polymers, Eudragit L100, shellac, polyvinyl acetate phthalate, cellulose acetate phthalate, hydroxypropyl methylcellulose acetate phthalate and hydroxypropyl methylcellulose (HPMC) was determined. Polymer films containing omeprazole were prepared by casting and characterized using powder X-ray diffractometry, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Omeprazole powder recrystallized from all solvents studied were similar to the original powder. The drug existed as the amorphous form in the five acid polymers whereas its crystalline form appeared in nonionic polymer HPMC. No evidence of a drug-polymer interaction was found. Omeprazole exists in amorphous form in polymers most commonly used in enteric filmcoated formulations.
{"title":"Crystallinity of Omeprazole in Various Film Polymers","authors":"N. Sarisuta, M. Kumpugdee","doi":"10.1211/146080800128735403","DOIUrl":"https://doi.org/10.1211/146080800128735403","url":null,"abstract":"The crystallinity of omeprazole in six film-forming polymers, Eudragit L100, shellac, polyvinyl acetate phthalate, cellulose acetate phthalate, hydroxypropyl methylcellulose acetate phthalate and hydroxypropyl methylcellulose (HPMC) was determined. Polymer films containing omeprazole were prepared by casting and characterized using powder X-ray diffractometry, Fourier transform infrared spectroscopy, and differential scanning calorimetry. Omeprazole powder recrystallized from all solvents studied were similar to the original powder. The drug existed as the amorphous form in the five acid polymers whereas its crystalline form appeared in nonionic polymer HPMC. No evidence of a drug-polymer interaction was found. Omeprazole exists in amorphous form in polymers most commonly used in enteric filmcoated formulations.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"19 1","pages":"7-11"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90147694","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 : 2000-01-01DOI: 10.1111/J.2042-7158.2000.TB00212.X
J. Guillon, S. Stiebing, M. Robba
The first synthesis of N-(4-fluorophenyl)-5-(4-fluorophenyl)-2-(4-hydroxybenzyl)pentanamide and a new synthesis of 1-(4-fluorophenyl)-3-[(4-fluorophenyl)propyl]-4-(4-hydroxyphenyl)-2-azetidinone starting from 4-fluorobenzaldehyde are described. This new amide could represent a potential new cholesterol absorption inhibitor.
{"title":"First Synthesis of N-(4-Fluorophenyl)-5-(4-fluorophenyl)-2-(4-hydroxybenzyl)pentanamide, a New Potential Cholesterol Absorption Inhibitor","authors":"J. Guillon, S. Stiebing, M. Robba","doi":"10.1111/J.2042-7158.2000.TB00212.X","DOIUrl":"https://doi.org/10.1111/J.2042-7158.2000.TB00212.X","url":null,"abstract":"The first synthesis of N-(4-fluorophenyl)-5-(4-fluorophenyl)-2-(4-hydroxybenzyl)pentanamide and a new synthesis of 1-(4-fluorophenyl)-3-[(4-fluorophenyl)propyl]-4-(4-hydroxyphenyl)-2-azetidinone starting from 4-fluorobenzaldehyde are described. This new amide could represent a potential new cholesterol absorption inhibitor.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"1 1","pages":"25-29"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90167916","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 : 2000-01-01DOI: 10.1211/146080800128735449
C. Bailey, S. Bates, S. L. Turner, M. Rossi, I. Morgan, S. Bloom
The adipocyte hormone leptin, a potential treatment for obesity, increases glucose uptake by skeletal muscle of normal rodents, mediated mainly via the central nervous system. This study investigates whether leptin affects glucose uptake by skeletal muscle of insulin resistant obese-diabetic ob/ob mice which do not produce functional leptin. Uptake of 2-deoxyglucose by isolated soleus muscles of ob/ob mice was unaltered by incubation with leptin (10−9M), with or without insulin (10−6M). Administration of leptin (10μg, twice daily, i.p.) for 7 days approximately normalized food intake, plasma glucose and insulin concentration, and increased insulin-stimulated 2-deoxyglucose uptake by isolated soleus muscles. Similar effects resulted from pair-feeding, although the pair-feeding did not lower plasma insulin or body weight as much as leptin. The results suggest that leptin replacement in ob/ob mice reduces insulin resistance in skeletal muscle, and this effect is largely attributable to reduced food intake.
{"title":"Leptin Improves Insulin Sensitivity of Skeletal Muscle in Obese‐diabetic ob/ob Mice","authors":"C. Bailey, S. Bates, S. L. Turner, M. Rossi, I. Morgan, S. Bloom","doi":"10.1211/146080800128735449","DOIUrl":"https://doi.org/10.1211/146080800128735449","url":null,"abstract":"The adipocyte hormone leptin, a potential treatment for obesity, increases glucose uptake by skeletal muscle of normal rodents, mediated mainly via the central nervous system. This study investigates whether leptin affects glucose uptake by skeletal muscle of insulin resistant obese-diabetic ob/ob mice which do not produce functional leptin. Uptake of 2-deoxyglucose by isolated soleus muscles of ob/ob mice was unaltered by incubation with leptin (10−9M), with or without insulin (10−6M). Administration of leptin (10μg, twice daily, i.p.) for 7 days approximately normalized food intake, plasma glucose and insulin concentration, and increased insulin-stimulated 2-deoxyglucose uptake by isolated soleus muscles. Similar effects resulted from pair-feeding, although the pair-feeding did not lower plasma insulin or body weight as much as leptin. The results suggest that leptin replacement in ob/ob mice reduces insulin resistance in skeletal muscle, and this effect is largely attributable to reduced food intake.","PeriodicalId":19946,"journal":{"name":"Pharmacy and Pharmacology Communications","volume":"5 1","pages":"35-39"},"PeriodicalIF":0.0,"publicationDate":"2000-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78407501","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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