Rational Design of a Combination Medication for the Treatment of Obesity

@article{Greenway2009RationalDO,
  title={Rational Design of a Combination Medication for the Treatment of Obesity},
  author={Frank L. Greenway and Martha Jo Whitehouse and Maria Guttadauria and James W. Anderson and Richard L. Atkinson and Ken Fujioka and Kishore M Gadde and Alok K. Gupta and Patrick M O'Neil and Donald Schumacher and D K Smith and Eduardo Dunayevich and Gary D. Tollefson and Eckard San Diego Weber and Michael A. Cowley},
  journal={Obesity},
  year={2009},
  volume={17}
}
Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau. [] Key Method In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin (POMC) neurons in mouse brain. A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice.
View on Wiley
onlinelibrary.wiley.com
265 Citations
Highly Influential Citations
18
Background Citations
92
Methods Citations
5
Results Citations
7

265 Citations

Comparison of combined bupropion and naltrexone therapy for obesity with monotherapy and placebo.

NB caused gradual sustained weight loss over 48 wk; NB32 and NB16 demonstrated greater weight loss in the intent-to-treat population due to lower attrition rates; further study is needed to demonstrate long-term efficacy and safety of NB.

Naltrexone HCI/bupropion HCI for chronic weight management in obese adults: patient selection and perspectives

  • C. Tek
  • Biology, Medicine
    Patient preference and adherence
  • 2016
The rationale for the suggested patient selection and clinical strategies for special patient populations are discussed, and the naltrexone–bupropion combination seems to be quite effective for 6-month and 1-year outcomes for clinically significant weight loss.

Combination therapy with naltrexone and bupropion for obesity

When used in conjunction with diet and exercise, the naltrexone/bupropion combination may be a useful treatment option for obesity, especially for overweight and obese adults who report difficulty controlling eating behavior and their response to food cravings.

Centrally Acting Agents for Obesity: Past, Present, and Future

A review of central nervous system acting anti-obesity drugs evaluates current therapies such as phentermine/topiramate, which act through multiple neurotransmitter pathways to reduce appetite and future drugs include tesofensine, a potent triple reuptake inhibitor in Phase III trials for obesity, and semaglutide, an oral GLP-1 analog approved for diabetes and currently in trials for Obesity.

Naltrexone/bupropion for obesity: an investigational combination pharmacotherapy for weight loss.

Effects of acute low-dose combined treatment with rimonabant and sibutramine on appetite and weight gain in rats

Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial

Drug safety evaluation of naltrexone/bupropion for the treatment of obesity

Naltrexone/bupropion has a greater weight loss efficacy than two FDA-approved medications, orlistat and lorcaserin and phentermine/topiramate, and has no abuse potential.

Combination therapy with naltrexone and bupropion for

When used in conjunction with diet and exercise, the naltrexone/bupropion combination may be a useful treatment option for obesity, especially for overweight and obese adults who report difficulty controlling eating behavior and their response to food cravings.

Sibutramine & naloxone: Infra-additive interaction in the regulation of appetite?

...

References

SHOWING 1-10 OF 50 REFERENCES

Effects of long‐term therapy with naltrexone on body weight in obesity

The effects of naltrexone on weight loss were less than expected in light of prior animal studies, but further studies with a wider dose range of nALTrexone may be indicated.

Inhibition of Dopamine and Norepinephrine Reuptake Produces Additive Effects on Energy Balance in Lean and Obese Mice

It is demonstrated that combined DA and NE reuptake inhibition produces additive effects on energy balance in lean and obese mice on both standard and high-fat diet, providing a foundation for further research on the effects of BUP and similar compounds on energy Balance in mice.

A controlled trial of naltrexone in obese humans.

In the present study naltrexone at a daily dosage of 200 mg did not appear to have efficacy in producing weight loss after eight weeks of treatment, and studies of the effects of naltaxone at higher dosage or for longer periods should monitor hepatic function.

Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial.

Bupropion SR 300 and 400 mg/d were well-tolerated by obese adults and were associated with a 24-week weight loss of 7.2% and 10.1% and sustained weight losses at 48 weeks.

Naltrexone reduces weight gain, alters “β-endorphin”, and reduces insulin output from pancreatic islets of genetically obese mice

A double-blind clinical trial in weight control. Use of fenfluramine and phentermine alone and in combination.

Combining fenfluramine and phentermine capitalized on their pharmacodynamic differences, resulting in equivalent weight loss, fewer adverse effects, and better appetite control.

Bupropion: a review of its mechanism of antidepressant activity.

The mechanism of action of buPropion appears to have an unusual, not fully understood, noradrenergic link, and the mild central nervous system activating effects of bupropion appear to be due to weak dopaminergic mechanisms.

Diet-induced obesity causes severe but reversible leptin resistance in arcuate melanocortin neurons.

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

The results of this study suggest that the mild weight loss effect of BUP in humans may be due to increased locomotion or heat production, and inhibition of DA+NE reuptake (with GBR+NIS) increased energy expenditure without a compensatory increase in food intake, supporting a role for novel combination catecholamine reuptakes inhibitors in pharmacotherapy for obesity.

Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus

An integrated model of leptin action and neuronal architecture in the arcuate nucleus of the hypothalamus is proposed and it is shown that melanocortin peptides have an autoinhibitory effect on this circuit.