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These researchers suspected that the cardiac effects of amphetamines could have a cephalic origin, suggesting the possibility of developing a similar drug, but which does not cross the blood-brain barrier, thus avoiding side effects, but preserving the action against obesity.
To test this hypothesis, they linked polymer chains of polyethylene glycol (PEG) to amphetamine, a process known as pegylation.
“Pegylation is often used to mask recognition drugs by the immune system or to increase the hydrodynamic size of molecules by changing their distribution throughout the body,” said Gonçalo Bernardes.
Through this process, the researchers created a larger-than-original pegylated amphetamine, which they called pegyamph, designed not to penetrate the blood-brain barrier, “which was proven by testing for its absence in the brain of mice treated with this drug. , and that consequently it did not present food suppression or increase of locomotion “.
This lack of behavioral effects is further confirmation that the pegyamph cannot even cross the blood-brain barrier, the IGC emphasized.
The team also used different routes of administration (intracerebral and peripheral) to confirm that the cardiovascular effects of amphetamines originate in the brain. They found that both drugs, if administered directly to the brain, induce cardiovascular effects. On the other hand, and unlike amphetamine, these harmful side effects disappear when pegyamph, which does not act on the brain, is administered systemically through the peripheral route.
“The new drug has several advantages over existing amphetamine-based treatments for weight loss,” the IGC emphasized, citing, for example, the fact that, by not crossing the blood-brain barrier, pegyamph is not addictive and It also does not affect cardiovascular function, avoiding the harmful side effects that amphetamines can cause.
