AOD9604 and hGH appear to act in a similar manner to induce their effects on body weight regulation and adipose tissue mass in vivo. However, in vitro studies have demonstrated a number of differences suggesting that the two compounds operate via unique signaling pathways to control the regulation of theβ 3-AR. These studies suggested that AOD9604 had no interaction with the β3-AR or hGH receptors (11).
Just as you could eat more calories than you think if you aren’t keeping track, you might miss some positive results of your efforts if you aren’t tracking your progress. Weigh yourself weekly. Take body measurements of your waist, legs, chest, and arms every other week. Measure your body fat percentage. Take photos of yourself once a month. Sometimes the scale won’t show results from week to week, but if you have all of the other methods of tracking in place, you’ll be able to see your efforts are being rewarded.
Human Growth Hormone (hGH) is not only important for growth processes during childhood, but plays a pivotal role in lipid metabolism throughout life. It is well known that hGH is involved in the regulation of lipolysis and lipogenesis. Therefore, hGH was implicated as a good potential candidate for the treatment of obesity. However undesired side effects, such as induction of glucose intolerance and insulin resistance, diabetes, acromegaly, cancer, edema, and hypertension [10-13] rendered therapeutic doses of hGH unsuitable for long-term treatments in humans.
The medicines delegate referred the proposal to upschedule paracetamol/ibuprofen from Schedule 2 to Schedule 3 to the Advisory Committee on Medicines Scheduling (ACMS) in early 2011. The proposal was submitted by the Advisory Committee on Non-Prescription Medicines (ACNM) as they were currently assessing a product in which the sponsor did not satisfactorily establish the efficacy and safety of the product and that public health concerns raised during the assessment of the product could be addressed by access to a pharmacist. AFT Pharmaceuticals had submitted a product application with the TGA at the time of this item being considered by the delegate and ACMS.
These findings suggest that the acute effects of AOD9604 are quite different from the chronic effects. Enhancedβ 3-AR expression appears to play a major role in the chronic effectiveness of the compound in terms of fat metabolism and weight loss. The acute effects observed in this study confirm that the β3-AR is not the sole mediator of this action. The increase in β3-AR expression in response to hGH and AOD9604 would permit enhanced lipolytic sensitivity. Identification of the components of the intracellular pathway(s) and effector(s) activated by AOD9604 are currently being investigated. The results presented in this paper suggest that the effectiveness of AOD9604 and hGH may partly rely on their ability to increase levels of β3-AR RNA expression in models of obesity in which the numbers of the lipolytic receptor are low. These unique properties may give AOD9604 an advantage over other lipolytic agonists such as adrenergic agents and hGH, which exhibit undesirable side effects when administered chronically (22).
Paracetamol/caffeine formulations have a long-established safety and efficacy profile over 25 years of use as an open-sale medicine in major markets around the world. The paracetamol/caffeine combination analgesic was registered as a schedule 2 product in Australia and has been marketed since 2010. Since that time no new significant issues or potential risks have been reported.
The nature of the response to both hGH and AOD9604 is not clearly understood. We hypothesized that both molecules may influence the expression of the β3-adrenergic receptors (β3-ARs), the major lipolytic receptor in fat tissue. Both AOD9604 and hGH can increase β3-AR mRNA expression, as well as protein levels and function, in mouse and human cell lines in vitro (11). This response was investigated at the level of RNA and protein expression and function. The results for each mode of analysis were consistent in that both hGH and AOD9604 acted in a dose- and time-dependent manner to modulate the β3-AR response.
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