New Drug Suppresses Opioid-induced Respiratory Depression

The intravenous respiratory stimulant GAL-021 is effective in treating opioid-induced respiratory depression, according to the results of a small study.

A study in Anesthesiology deemed an intravenous respiratory stimulant named GAL-021 as effective in treating opioid-induced respiratory depression (OIRD).

Opioid medications, such as oxycodone, methadone, and fentanyl, are commonly used to relieve pre- and postoperative pain. However, these medications come with side effects including respiratory depression, which possibly leads to brain damage, cardiac arrest, and death, according to lead author Albert Dahan, MD, a professor of anesthesiology at Leiden University Medical Center in the Netherlands.

Intended to control breathing patterns, GAL-021 blocks the brain’s calcium-activated potassium channels. In a previous study conducted on animal models, GAL-021 was found to increase ventilatory drive and counteracted opioid-induced respiratory depression, without negatively affecting opioid-related pain relief. Though serotonin and dopamine receptor ligands were identified as effective targets for improving animals’ respiratory capabilities, these results could not be reciprocated in humans.

For a double-blind, randomized, and placebo-controlled crossover study, a team of researchers at Leiden University and Galleon Pharmaceuticals Corporation administered GAL-021 to 12 healthy males between the ages of 18 and 45 years, who were instructed to fast for 6 hours prior to the drug’s administration. The effects of OIRD were induced by giving patients low- and high-dose alfentanil on 2 separate occasions, which decreased their breathing capacity by decreased 25% to 30%.

Candidates with a history of a major medical or psychiatric disease or alcohol abuse, who consumed greater than 6 servings of caffeine daily, smoked within the last year, and had taken other investigational drugs within 3 months prior to inclusion were eliminated from the study.

Upon being given GAL-021, the researchers noted all of the patients experienced improved respiratory rate and tidal volume, without affecting blood pressure, cardiac output, pain threshold, and sedation.

Additionally, the investigators observed limited side effects in subjects who took GAL-021, with a few patients experiencing nausea and itching.

However, the production of a painkiller that doesn’t negative effect on respiration is still in the distant future, according to Dahan.

“Using an add-on drug that reverses or prevents respiratory depression caused by opioid use, without affecting pain relief, is currently our best option to treat this condition,” Dahan said in a statement. “While our data suggest that GAL-021 is an attractive alternative to other respiratory stimulants, additional studies are needed to further confirm these findings.”