"Thick" amphetamine
Historically, amphetamine-like medications, such as FDA-approved phentermine, have been among the most popular anti-obesity medications ever prescribed to patients. Acting on the central nervous system, they suppress appetite, but, unfortunately, are addictive and can cause dangerous side effects – tachycardia, hypertension and hyperthermia.
A group of Portuguese researchers led by Ana Domingos from the Gulbenkian de Ciencia Institute and Gonzalo Bernardes from the Institute of Molecular Medicine (Lisbon) modified amphetamine so that it does not enter the brain and does not cause the associated known side effects.
Despite the official recognition of obesity as a chronic disease, there are very few cost-effective ways to treat it with a long-term effect. One of them are drugs from the group of amphetamines. They act in the brain, reducing appetite, stimulating motor activity and increasing endurance. Unfortunately, these drugs strongly activate the sympathetic nervous system, as a result of which the heart rate accelerates, blood vessels narrow and blood pressure rises. In other words, amphetamines are sympathomimetics.
It has always been believed that the harmful effects of amphetamine on the cardiovascular system are the result not of a central action, but of direct stimulation of the sympathetic nerves of the heart. However, the researchers suspected that the side effects of amphetamines may actually occur in the brain. And if they were able to develop a drug that would not overcome the blood-brain barrier, undesirable effects could be avoided while maintaining the anti-obesity effect.
To test their hypothesis, the authors attached polyethylene glycol (PEG) polymer chains to amphetamine. The result was a large-molecular pegylated amphetamine (PEGyAMPH). Because of its larger size, PEGyAMPH could not penetrate the blood-brain barrier, and scientists proved this: it was absent in the brains of mice receiving PEGyAMPH. They also had neither suppressed appetite nor increased mobility. This lack of behavioral effects was another confirmation that PEGyAMPH does not really pass through the blood-brain barrier.
PEGyAMPH retained the ability to trigger the activation of sympathetic neurons and increase peripheral sympathetic output to adipose tissues. Researchers have demonstrated that PEGyAMPH protects mice from obesity, despite the absence of behavioral effects.
The new drug has several advantages over traditional amphetamines for weight loss. Since PEGyAMPH does not pass the blood-brain barrier, it is not addictive and does not affect cardiovascular function, which avoids side effects. In addition, it also normalized the blood glucose levels of mice by increasing insulin sensitivity, preventing hyperinsulinemia – a condition that precedes the development of type 2 diabetes. Thus, PEGyAMPH fights obesity with an efficiency comparable to AMPH, but with a clear mechanism that prevents effects affecting brain function by suppressing calorie intake by increasing energy expenditure.
Obesity is a serious health problem worldwide and is associated with many serious diseases, such as diabetes mellitus, heart disease and cancer. Although PEGyAMPH is only undergoing preclinical trials, this new weight loss drug offers hope for a safer and more cost-effective treatment than those currently available.
The technology is patented by the authors.
Article I.Mahu et al. Brain-Sparing Sympathofacilitators Mitigate Obesity without Adverse Cardiovascular Effects published in the journal Cell Metabolism.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Gulbenkian Science: Burning fat with brain-sparing amphetamines without harmful side effects.