Obesity is a major health issue across the world and is implicated in many serious health conditions such as diabetes, heart disease and cancer. Despite being officially declared a chronic disease, there are very few long-lasting and cost-effective treatments for obesity. Historically, amphetamine (AMPH) class drugs have been some of the most popular anti-obesity drugs to be prescribed and are widely considered to be the most effective while also being among the cheapest to produce. They work in the brain to reduce appetite and increase locomotion or stamina. However, these drugs are also known for strongly activating the sympathetic nervous system, the peripheral part of the nervous system known to accelerate the heart rate, constrict blood vessels and raise blood pressure. Consequently, they can present side effects such as dangerously increased heart rate and hypertension.
A research team led by Department of Physiology, Anatomy & Genetics Associate Professor Ana Domingos and Dr Gonçalo Bernardes (University of Cambridge) suspected that the cardiac side effects of amphetamines could originate in the brain. If this was the case, they hypothesised that if they could design a drug that did not pass the blood-brain barrier, they could avoid these unwanted outcomes, while perhaps retaining an anti-obesity action. In a new paper published in Cell Metabolism, the team have shown that the cardiac side effects of AMPH do indeed originate in the brain and have presented a modified amphetamine that does not enter the brain while avoiding its known side effects.