Abstract
Background: Abuse of analgesic and sedative drugs often leads to severe respiratory depression and sometimes death. Approximately 69,000 people worldwide die annuallyfrom opioid overdoses. Purpose: This work aimed to investigate whether CX1739 can be used for emergency treatment of acute respiratory depression due to drug abuse. Results: First, theresults clarify that CX1739 is a low-impact ampakine that can safely activate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors without causing excito-neurotoxicity. Second, CX1739 rapidly crossed the blood-brain barrier (Tmax=2min), which meets the requirement of rapid onset of action in vivo. Our work providespreliminarily confirmation that high-dose intravenous administration of CX1739 can immediately reverse respiratory depression in animal models of respiratory depression caused by opioid agonist 030418, pentobarbital sodiumand ethanol.
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