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Neurochemical Variants Could Be Safer Alternative To Morphine

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Opioid

While opioids are highly effective at treating chronic and severe pain, they carry a high risk of dependency due to their addictive nature.

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February 1, 2016 | by Sarah Massey, M.Sc.

According to researchers at Tulane University and Southeast Louisiana Veterans Health Care System, an analog of the neurochemical endomorphin could be just as effective as morphine at treating pain, without the addictive qualities of the drug. The results of the study were published in the journal, Neuropharmacology.

James Zadina, VA senior research career scientist and professor of medicine, pharmacology and neuroscience at Tulane University School of Medicine, and his colleagues synthesized a number of endomorphin analogues – a neurochemical that is naturally found in the body – and tested them for safety and effectiveness in mice. Endomorphin and morphine act on the same opioid receptor in the brain to release pain in the body.

While opioids are highly effective at treating chronic and severe pain, they carry a high risk of dependency due to their addictive nature. Opium-derived drugs can also cause motor impairment and respiratory depression leading to thousands of overdose-related deaths in the US each year. The dosage of opioid drugs must also be increased over time due to the tendency for patients to develop a tolerance to the drug, which increases the risk of potential drug abuse and overdose.

“These side effects were absent or reduced with the new drug,” said Zadina. “It's unprecedented for a peptide to deliver such powerful pain relief with so few side effects.”



The researchers found that the peptide-based endomorphin analogue provided sustained pain relief in rats without significantly affecting respiratory rates. When compared to a similar dose of morphine, the rats displayed substantially lower breathing rates.

In addition, the new drug did not affect motor coordination, which often affects elderly patients taking opioids such as morphine. The drug did not contribute to the development of drug tolerance by activating spinal glial cells – an inflammation response characteristic of morphine tolerance.

The researchers conducted multiple tests in order to determine whether the new drug would have addictive qualities. In one test, rats who were given morphine would spend more time in the place where the morphine was administered, while the endomorphin drug did not elicit the same response.

When rats were trained to press a lever that dispensed the drug, they only focused their efforts on obtaining morphine and not the new drug. According to Zadina, these results could be predictive of the effects of the drug on humans, and he plans to start human clinical trials within the next two years.

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Keywords: Opioid, Drug Abuse, Drug Development


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