Anorectic efficacy and safety of the diethylpropion‐topiramate combination in rats
Preclinical Research & Development Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary mechanisms of action at lower doses may produce a greater efficacy with a better safety profile. This study was designed to asses...
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| Veröffentlicht in: | Drug development research 2018-08, Vol.79 (5), p.225-233 |
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| creator | Cortés‐Moreno, Gabriela Y. Roa‐Coria, José E. Zúñiga‐Romero, Ángel Huerta‐Cruz, Juan C. Lara‐Padilla, Eleazar del Valle‐Laisequilla, Cecilia F. Rocha‐González, Héctor I. Reyes‐García, Juan G. |
| description | Preclinical Research & Development
Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary mechanisms of action at lower doses may produce a greater efficacy with a better safety profile. This study was designed to assess the anorectic effect and safety of a diethylpropion + topiramate mixture in rats. The anorectic effect of drugs was measured using a sweetened milk consumption model, and the corresponding interaction was determined by isobolographic analysis, interaction index and confidence intervals. Additionally, blood pressure was measured using a sphygmomanometer in the rat tail. Diethylpropion and topiramate alone or in combination increased the anorectic effect in a dose‐dependent fashion in either nondeprived or 12 hr food‐deprived rats. All theoretical ED30 values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED30 values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED30 of diethylpropion + topiramate combination did not affect the blood pressure. Data suggests that low doses of the diethylpropion + topiramate combination can potentiate the anorectic effect of individual drugs with a better safety profile, which deserves further investigation in clinical trials. |
| doi_str_mv | 10.1002/ddr.21434 |
| format | Article |
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Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary mechanisms of action at lower doses may produce a greater efficacy with a better safety profile. This study was designed to assess the anorectic effect and safety of a diethylpropion + topiramate mixture in rats. The anorectic effect of drugs was measured using a sweetened milk consumption model, and the corresponding interaction was determined by isobolographic analysis, interaction index and confidence intervals. Additionally, blood pressure was measured using a sphygmomanometer in the rat tail. Diethylpropion and topiramate alone or in combination increased the anorectic effect in a dose‐dependent fashion in either nondeprived or 12 hr food‐deprived rats. All theoretical ED30 values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED30 values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED30 of diethylpropion + topiramate combination did not affect the blood pressure. Data suggests that low doses of the diethylpropion + topiramate combination can potentiate the anorectic effect of individual drugs with a better safety profile, which deserves further investigation in clinical trials.</description><identifier>ISSN: 0272-4391</identifier><identifier>EISSN: 1098-2299</identifier><identifier>DOI: 10.1002/ddr.21434</identifier><identifier>PMID: 30188585</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Animals ; anorectic ; Appetite Depressants - administration & dosage ; Appetite Depressants - adverse effects ; Blood pressure ; Blood Pressure - drug effects ; Clinical trials ; Confidence intervals ; Dietary restrictions ; diethylpropion ; Diethylpropion - administration & dosage ; Diethylpropion - adverse effects ; Dose-Response Relationship, Drug ; Drug dosages ; Drug Synergism ; Drugs ; Effectiveness ; Humans ; isobologram ; Male ; Medical research ; Milk ; obesity ; Rats ; Rats, Wistar ; Safety ; Topiramate ; Topiramate - administration & dosage ; Topiramate - adverse effects</subject><ispartof>Drug development research, 2018-08, Vol.79 (5), p.225-233</ispartof><rights>2018 Wiley Periodicals, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3534-1db26750dbd4f063a34e1c38230eb025aaff997e04b151de66db73e566cf354b3</citedby><cites>FETCH-LOGICAL-c3534-1db26750dbd4f063a34e1c38230eb025aaff997e04b151de66db73e566cf354b3</cites><orcidid>0000-0002-7524-9375</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fddr.21434$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fddr.21434$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30188585$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cortés‐Moreno, Gabriela Y.</creatorcontrib><creatorcontrib>Roa‐Coria, José E.</creatorcontrib><creatorcontrib>Zúñiga‐Romero, Ángel</creatorcontrib><creatorcontrib>Huerta‐Cruz, Juan C.</creatorcontrib><creatorcontrib>Lara‐Padilla, Eleazar</creatorcontrib><creatorcontrib>del Valle‐Laisequilla, Cecilia F.</creatorcontrib><creatorcontrib>Rocha‐González, Héctor I.</creatorcontrib><creatorcontrib>Reyes‐García, Juan G.</creatorcontrib><title>Anorectic efficacy and safety of the diethylpropion‐topiramate combination in rats</title><title>Drug development research</title><addtitle>Drug Dev Res</addtitle><description>Preclinical Research & Development
Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary mechanisms of action at lower doses may produce a greater efficacy with a better safety profile. This study was designed to assess the anorectic effect and safety of a diethylpropion + topiramate mixture in rats. The anorectic effect of drugs was measured using a sweetened milk consumption model, and the corresponding interaction was determined by isobolographic analysis, interaction index and confidence intervals. Additionally, blood pressure was measured using a sphygmomanometer in the rat tail. Diethylpropion and topiramate alone or in combination increased the anorectic effect in a dose‐dependent fashion in either nondeprived or 12 hr food‐deprived rats. All theoretical ED30 values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED30 values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED30 of diethylpropion + topiramate combination did not affect the blood pressure. Data suggests that low doses of the diethylpropion + topiramate combination can potentiate the anorectic effect of individual drugs with a better safety profile, which deserves further investigation in clinical trials.</description><subject>Animals</subject><subject>anorectic</subject><subject>Appetite Depressants - administration & dosage</subject><subject>Appetite Depressants - adverse effects</subject><subject>Blood pressure</subject><subject>Blood Pressure - drug effects</subject><subject>Clinical trials</subject><subject>Confidence intervals</subject><subject>Dietary restrictions</subject><subject>diethylpropion</subject><subject>Diethylpropion - administration & dosage</subject><subject>Diethylpropion - adverse effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug dosages</subject><subject>Drug Synergism</subject><subject>Drugs</subject><subject>Effectiveness</subject><subject>Humans</subject><subject>isobologram</subject><subject>Male</subject><subject>Medical research</subject><subject>Milk</subject><subject>obesity</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Safety</subject><subject>Topiramate</subject><subject>Topiramate - administration & dosage</subject><subject>Topiramate - adverse effects</subject><issn>0272-4391</issn><issn>1098-2299</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMlKBTEQRYMo-hwW_oAE3OiiNVMPWYozCILoOqSTCkZ6eCZ5SO_8BL_RLzH61IXgqgrq1OVyENql5IgSwo6tDUeMCi5W0IwS2RSMSbmKZoTVrBBc0g20GeMTIZSKpllHG5zQpimbcobuT4YxgEneYHDOG20mrAeLo3aQJjw6nB4BWw_pcermYZz7cXh_fUt5CbrXCbAZ-9YPOuUD9gMOOsVttOZ0F2Hne26hh4vz-9Or4ub28vr05KYwvOSioLZlVV0S21rhSMU1F0ANbxgn0BJWau2clDUQ0dKSWqgq29Ycyqoyjpei5VvoYJmbiz0vICbV-2ig6_QA4yIqlu1wVueHjO7_QZ_GRRhyO8WIlJJxJnimDpeUCWOMAZyaB9_rMClK1KdqlVWrL9WZ3ftOXLQ92F_yx20GjpfAi-9g-j9JnZ3dLSM_ACkliJ4</recordid><startdate>201808</startdate><enddate>201808</enddate><creator>Cortés‐Moreno, Gabriela Y.</creator><creator>Roa‐Coria, José E.</creator><creator>Zúñiga‐Romero, Ángel</creator><creator>Huerta‐Cruz, Juan C.</creator><creator>Lara‐Padilla, Eleazar</creator><creator>del Valle‐Laisequilla, Cecilia F.</creator><creator>Rocha‐González, Héctor I.</creator><creator>Reyes‐García, Juan G.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-7524-9375</orcidid></search><sort><creationdate>201808</creationdate><title>Anorectic efficacy and safety of the diethylpropion‐topiramate combination in rats</title><author>Cortés‐Moreno, Gabriela Y. ; Roa‐Coria, José E. ; Zúñiga‐Romero, Ángel ; Huerta‐Cruz, Juan C. ; Lara‐Padilla, Eleazar ; del Valle‐Laisequilla, Cecilia F. ; Rocha‐González, Héctor I. ; Reyes‐García, Juan G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3534-1db26750dbd4f063a34e1c38230eb025aaff997e04b151de66db73e566cf354b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Animals</topic><topic>anorectic</topic><topic>Appetite Depressants - administration & dosage</topic><topic>Appetite Depressants - adverse effects</topic><topic>Blood pressure</topic><topic>Blood Pressure - drug effects</topic><topic>Clinical trials</topic><topic>Confidence intervals</topic><topic>Dietary restrictions</topic><topic>diethylpropion</topic><topic>Diethylpropion - administration & dosage</topic><topic>Diethylpropion - adverse effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug dosages</topic><topic>Drug Synergism</topic><topic>Drugs</topic><topic>Effectiveness</topic><topic>Humans</topic><topic>isobologram</topic><topic>Male</topic><topic>Medical research</topic><topic>Milk</topic><topic>obesity</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Safety</topic><topic>Topiramate</topic><topic>Topiramate - administration & dosage</topic><topic>Topiramate - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cortés‐Moreno, Gabriela Y.</creatorcontrib><creatorcontrib>Roa‐Coria, José E.</creatorcontrib><creatorcontrib>Zúñiga‐Romero, Ángel</creatorcontrib><creatorcontrib>Huerta‐Cruz, Juan C.</creatorcontrib><creatorcontrib>Lara‐Padilla, Eleazar</creatorcontrib><creatorcontrib>del Valle‐Laisequilla, Cecilia F.</creatorcontrib><creatorcontrib>Rocha‐González, Héctor I.</creatorcontrib><creatorcontrib>Reyes‐García, Juan G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Drug development research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cortés‐Moreno, Gabriela Y.</au><au>Roa‐Coria, José E.</au><au>Zúñiga‐Romero, Ángel</au><au>Huerta‐Cruz, Juan C.</au><au>Lara‐Padilla, Eleazar</au><au>del Valle‐Laisequilla, Cecilia F.</au><au>Rocha‐González, Héctor I.</au><au>Reyes‐García, Juan G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anorectic efficacy and safety of the diethylpropion‐topiramate combination in rats</atitle><jtitle>Drug development research</jtitle><addtitle>Drug Dev Res</addtitle><date>2018-08</date><risdate>2018</risdate><volume>79</volume><issue>5</issue><spage>225</spage><epage>233</epage><pages>225-233</pages><issn>0272-4391</issn><eissn>1098-2299</eissn><abstract>Preclinical Research & Development
Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary mechanisms of action at lower doses may produce a greater efficacy with a better safety profile. This study was designed to assess the anorectic effect and safety of a diethylpropion + topiramate mixture in rats. The anorectic effect of drugs was measured using a sweetened milk consumption model, and the corresponding interaction was determined by isobolographic analysis, interaction index and confidence intervals. Additionally, blood pressure was measured using a sphygmomanometer in the rat tail. Diethylpropion and topiramate alone or in combination increased the anorectic effect in a dose‐dependent fashion in either nondeprived or 12 hr food‐deprived rats. All theoretical ED30 values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED30 values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED30 of diethylpropion + topiramate combination did not affect the blood pressure. Data suggests that low doses of the diethylpropion + topiramate combination can potentiate the anorectic effect of individual drugs with a better safety profile, which deserves further investigation in clinical trials.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>30188585</pmid><doi>10.1002/ddr.21434</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7524-9375</orcidid></addata></record> |
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| ispartof | Drug development research, 2018-08, Vol.79 (5), p.225-233 |
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| subjects | Animals anorectic Appetite Depressants - administration & dosage Appetite Depressants - adverse effects Blood pressure Blood Pressure - drug effects Clinical trials Confidence intervals Dietary restrictions diethylpropion Diethylpropion - administration & dosage Diethylpropion - adverse effects Dose-Response Relationship, Drug Drug dosages Drug Synergism Drugs Effectiveness Humans isobologram Male Medical research Milk obesity Rats Rats, Wistar Safety Topiramate Topiramate - administration & dosage Topiramate - adverse effects |
| title | Anorectic efficacy and safety of the diethylpropion‐topiramate combination in rats |
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