Using rats, scientists compared several engineered variants of the neurochemical endomorphin - found naturally in the body - to morphine to measure their effectiveness and side effects.
The peptide-based drugs target the same pain-relieving opioid receptor as morphine, according to scientists at Tulane University and Southeast Louisiana Veterans Health Care System in US.
Opium-based drugs are the leading treatments for severe and chronic pain, but they can be highly addictive. Their abuse results in thousands of overdose deaths in the US annually, researchers said.
"These side effects were absent or reduced with the new drug," said lead investigator James Zadina, professor at the Tulane University School of Medicine.
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"It's unprecedented for a peptide to deliver such powerful pain relief with so few side effects," said Zadina.
In the study, the new endomorphin drug produced longer pain relief without substantially slowing breathing in rats; a similarly potent dosage of morphine produced significant respiratory depression.
Impairment of motor coordination, which can be of particular importance to older adults, was significant after morphine but not with the endomorphin drug.
Scientists conducted several experiments to test whether the drug would be addictive. One showed that although rats would spend more time in a compartment where they had received morphine, the new drug did not affect this behaviour.
Another test showed that when the press of a bar produced an infusion of drug, the rats only increased efforts to obtain morphine and not the new drug. The tests are predictive of human drug abuse, Zadina said.
The study was published in the journal Neuropharmacology.