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Behavioural Pharmacology Aug 2021Drug combinations are being studied as potential therapies to increase the efficacy or improve the safety profile of weight loss medications. This study was designed to...
Drug combinations are being studied as potential therapies to increase the efficacy or improve the safety profile of weight loss medications. This study was designed to determine the anorectic interaction and safety profile of 5-hydroxytryptophan (5-HTP)/carbidopa + diethylpropion and 5-HTP/carbidopa + phentermine combinations in rats. The anorectic effect of individual drugs or in combination was evaluated by the sweetened milk test. Isobologram and interaction index were employed to determine the anorectic interaction between 5-HTP/carbidopa and diethylpropion or phentermine. Plasma serotonin (5-HT) was measured by ELISA. Safety of repeated doses of both combinations in rats was evaluated using the tail sphygmomanometer, cardiac ultrasound, hematic biometry and blood chemistry. A single oral 5-HTP, diethylpropion or phentermine dose increased the anorectic effect, in a dose-dependent fashion, in 12 h-fasted rats. A dose of carbidopa at 30 mg/kg reduced the 5-HTP-induced plasmatic serotonin concentration and augmented the 5-HTP-induced anorectic effect. Isobologram and interaction index indicated a potentiation interaction between 5-HTP/30 mg/kg carbidopa + diethylpropion and 5-HTP/30 mg/kg carbidopa + phentermine. Chronic administration of experimental ED40 of 5-HTP/30 mg/kg carbidopa + phentermine, but not 5-HTP/30 mg/kg carbidopa + diethylpropion, increased the mitral valve leaflets area. Moreover, there were no other significant changes in cardiovascular, hematic or blood parameters. Both combinations induced around 20% body weight loss after 3 months of oral administration. Results suggest that 5-HTP/30 mg/kg carbidopa potentiates the anorectic effect of diethylpropion and phentermine with an acceptable safety profile, but further clinical studies are necessary to establish their therapeutic potential in the obesity treatment.
Topics: 5-Hydroxytryptophan; Animals; Appetite Depressants; Biomarkers, Pharmacological; Carbidopa; Cardiovascular System; Diethylpropion; Drug Combinations; Drug Dosage Calculations; Drug Interactions; Drug Monitoring; Drug Therapy, Combination; Obesity; Phentermine; Rats
PubMed: 33660661
DOI: 10.1097/FBP.0000000000000625 -
Drug Development Research Aug 2018Preclinical Research & Development Current drugs for obesity treatment have limited efficacy and considerable adverse effects. Combination of drugs with complementary...
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 ED values of diethylpropion + topiramate combinations at 1:1, 1:3, and 3:1 dose ratios were significantly higher than experimental ED values. In addition, interaction indices and confidence intervals confirmed the potentiation between both drugs. Theoretical ED 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.
Topics: Animals; Appetite Depressants; Blood Pressure; Diethylpropion; Dose-Response Relationship, Drug; Drug Synergism; Humans; Male; Milk; Rats, Wistar; Topiramate
PubMed: 30188585
DOI: 10.1002/ddr.21434 -
Pharmacology, Biochemistry, and Behavior Feb 2009Diethylpropion (DEP) is a stimulant drug widely used for weight control in Brazil and other American countries. However, its effects on behavior and addiction potential...
Diethylpropion (DEP) is a stimulant drug widely used for weight control in Brazil and other American countries. However, its effects on behavior and addiction potential are not yet well known. Data suggest that sensitization resulting from pre-exposure to psychostimulants could be a possible risk factor in subsequent drug addiction. The purpose of this investigation was to verify whether pre-exposure to DEP would sensitize rats to the motor activating effect and to the rewarding value of DEP. Two experiments were conducted. In both experiments rats were pre-exposed to DEP (20 mg/kg) or vehicle for 7 consecutive days. The acute effect of DEP (0.0, 1.0, 2.5 or 5.0 mg/kg) on motor activity (Experiment 1) and induction of Conditioned Place Preference-CPP (Experiment 2) were then measured. Results from Experiment 1 showed that 2.5 and 5.0 mg/kg DEP increased motor activity. Sensitization of this motor effect was observed. In Experiment 2, the doses of 2.5 and 5.0 mg/kg DEP induced CPP, indicating their rewarding value. However, no sensitization effect was observed. The results suggest that DEP at low doses has psychostimulant and rewarding properties. It is recommended that more effort should be dedicated to elucidating DEP abuse potential.
Topics: Animals; Appetite Depressants; Body Weight; Central Nervous System Stimulants; Conditioning, Operant; Data Interpretation, Statistical; Diethylpropion; Male; Motor Activity; Rats; Rats, Wistar; Reward
PubMed: 18976683
DOI: 10.1016/j.pbb.2008.10.001 -
The British Journal of Psychiatry : the... Aug 1988
Topics: Antidepressive Agents; Bupropion; Diethylpropion; Humans; Propiophenones; Psychoses, Substance-Induced
PubMed: 3151278
DOI: 10.1192/bjp.153.2.265 -
The Australian and New Zealand Journal... Mar 1979The case of a 36-year old woman who developed a paranoid psychosis while abusing diethylpropion is reported. It is suggested that the newer appetite-suppressing drugs...
The case of a 36-year old woman who developed a paranoid psychosis while abusing diethylpropion is reported. It is suggested that the newer appetite-suppressing drugs have a bigger abuse potential than eas previously thought and may therefore be a hazard for a minority of susceptible subjects. The need to test separately for diethylpropion in cases of suspected drug-induced psychosis is emphasized.
Topics: Adult; Diethylpropion; Dose-Response Relationship, Drug; Female; Hallucinations; Humans; Obesity; Paranoid Disorders
PubMed: 288469
DOI: 10.3109/00048677909159112 -
The Journal of the College of General... May 1963
Topics: Diethylpropion; Humans; Obesity
PubMed: 14024264
DOI: No ID Found -
Drug and Therapeutics Bulletin Feb 1968
Topics: Diethylpropion; Humans; Substance-Related Disorders
PubMed: 5640914
DOI: No ID Found -
The Medical Journal of Australia Dec 1970
Topics: Adult; Diethylpropion; Female; Humans; Psychoses, Substance-Induced
PubMed: 5491087
DOI: 10.5694/j.1326-5377.1970.tb63365.x -
British Medical Journal Aug 1962
Topics: Appetite; Behavior, Addictive; Diethylpropion; Propiophenones; Substance-Related Disorders; Sympathomimetics
PubMed: 13879863
DOI: 10.1136/bmj.2.5302.456