A brain-targeted ampakine compound protects against opioid-induced respiratory depression

European Journal of Pharmacology
Wei DaiRui-Bin Su

Abstract

The use of opioid drugs for pain relief can induce life-threatening respiratory depression. Although naloxone effectively counteracts opioid-induced respiratory depression, it diminishes the efficacy of analgesia. Our studies indicate that ampakines, in particular, a brain-targeted compound XD-8-17C, are able to reverse respiratory depression without affecting analgesia at relatively low doses. Mice and rats were subcutaneously or intravenously injected with the opioid agonist TH-030418 to induce moderate or severe respiratory depression. XD-8-17C was intravenously administered before or after TH-030418. The effect of XD-8-17C on opioid-induced respiratory depression was evaluated in terms of the opioid-induced acute death rate, arterial blood gas analysis and pulmonary function tests. In addition, the hot-plate test was conducted to investigate whether XD-8-17C influenced opioid-induced analgesia. Pre-treatment with XD-8-17C significantly reduced opioid-induced acute death, and increased the median lethal dose of TH-030418 by 4.7-fold. Blood gas analysis and pulmonary function tests demonstrated that post-treatment with XD-8-17C alleviated respiratory depression, as indicated by restoration of arterial blood gas (pO2, sO2, cK+...Continue Reading

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Citations

Mar 20, 2018·Anesthesiology·Albert DahanMarieke Niesters
Dec 6, 2019·Peptides·Richard J Bodnar
Feb 12, 2021·Journal of Medicinal Chemistry·Ross S ManciniMark A Reed
Apr 18, 2020·ACS Chemical Neuroscience·Jillian L Kyzer, Cody J Wenthur
Dec 28, 2021·Anesthesiology·Rutger van der SchrierAlbert Dahan

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