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Anorectic efficacy and safety of the diethylpropion‐topiramate combination in rats
Author(s) -
CortésMoreno Gabriela Y.,
RoaCoria José E.,
ZúñigaRomero Ángel,
HuertaCruz Juan C.,
LaraPadilla Eleazar,
del ValleLaisequilla Cecilia F.,
RochaGonzález Héctor I.,
ReyesGarcía Juan G.
Publication year - 2018
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21434
Subject(s) - anorectic , topiramate , pharmacology , drug interaction , drug , medicine , body weight , epilepsy , psychiatry
Preclinical Research & DevelopmentCurrent 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 ED 30 values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED 30 values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED 30 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.