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Oct 8, 2020

The impact and mechanism of ampakine CX1739 on protection against respiratory depression in rats

Background

Abuse of analgesic and sedative drugs often leads to severe respiratory depression and sometimes death. Approximately 69,000 people worldwide die annually from 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, the results 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 = 2 min), which meets the requirement of rapid onset of action in vivo. Our work provides preliminarily 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 sodium and ethanol.

By Dian Xiao, Fei Xie, Xin Xu & Xinbo Zhou

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