Oct. 7, 2010 A new drug called repinotan blocks the respiratory depressant effects of morphine-like opioid drugs -- without altering their potent pain-relieving effects, according to a study in the October issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).
If the promising results of animal studies are borne out by future research, then repinotan could become an important part of safe, effective pain control after surgery. The new study was led by Dr. Ulf Guenther of University of Ulm, Germany.
Subcutaneous Oxygen Levels during Surgery Predicts Later Infection Risk The researchers performed a series of experiments to see how repinotan influenced the effects of morphine. Although morphine and related drugs (opioids) are highly effective in treating pain after surgery, they share a common characteristic: they decrease the drive to breathe. This is a potentially serious side effect that can limit the use of opioid drugs for pain control.
In the study, rats were given a morphine dose high enough to slow the breathing rate. When the animals were subsequently treated with repinotan, their respiratory rate rapidly returned toward normal.
At the same time, repinotan did not alter the pain-blocking effects of morphine. This is especially important because, although other drugs are available to reverse the respiratory depressant effects of opioids, they also reverse the pain-relieving effects.
There were no serious cardiovascular side effects with repinotan, although it did cause a drop in blood pressure.
"For years, investigators have tried to develop an opioid that produced the profound analgesia of morphine, but without the effects on breathing rate," explains Dr. Steven L. Shafer of Columbia University, Editor-in-Chief of Anesthesia & Analgesia. More recently, specific types of drugs have been developed that selectively reverse morphine-induced depression of breathing. Repinotan is the first drug of this type that has proven suitable for studies in humans.
"This is an incredibly exciting development in opioid pharmacology," Dr. Shafer adds. "A drug that blocks the ability of opioids to suppress breathing, while not interfering with the pain relief, would be a huge advance in pain management and patient safety. Unless the drug had other toxicities, such a drug would immediately become the standard of care for post-operative patients receiving opioids."
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- U. Guenther et al. Repinotan, a Selective 5-HT1A-R-Agonist, Antagonizes Morphine-Induced Ventilatory Depression in Anesthetized Rats. Anesthesia & Analgesia, 2010 DOI: 10.1213/%u200BANE.0b013e3181eac011
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