Biological mechanisms of respiratory depression induced by sedative-hypnotic anesthetics and related countermeasures
10.3867/j.issn.1000-3002.2025.08313
- VernacularTitle:镇静催眠麻醉类药物诱发呼吸抑制的生物学机制及其对抗策略
- Author:
Weijie TAO
1
;
Zheng YONG
;
Ruibin SU
Author Information
1. 河南大学药学院,河南 开封 475004;军事医学研究院,北京 100850
- Publication Type:Journal Article
- Keywords:
respiratory depression;
toxicological countermeasure;
opioids;
anesthetics;
benzodiaz-epines
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(6):453-461
- CountryChina
- Language:Chinese
-
Abstract:
Commonly used anesthetic sedatives(opioids,benzodiazepines,ketamine,propofol,etc.)share the risk of inducing respiratory depression,and their multi-target mechanism of action pres-ents significant heterogeneity.Opioids inhibit the rhythmic activity of the respiratory center of the medulla bulbar(such as the PreB?tzinger complex and parbrachial nucleus)by activating both the μ-opioid receptor and the G-protein-gated inwardly-rectifying potassium channel and β-arrestin signaling pathway,resulting in decreased respiratory frequency and amplitude.Benzodiazepines enhance inhibitory neurotransmis-sion mediated by γ-aminobutyric acid receptors,reduce the sensitivity of chemoreceptors to PaCO2 and PaO2,and lead to a decreased tidal volume and upper airway obstruction.Ketamine inhibits respiratory drive and respiratory muscle function by blocking N-methyl-D-aspartic acid receptors and indirectly affecting the μ-opioid receptor.In addition,propofol inhibits pre-expiratory neuronal activity and relaxes upper airway muscles by activating the GABAA receptor β3 subunit.Currently,specific antagonists(naloxone/flumazenil)and respiratory stimulants(doxapram)are clinically used to treat respiratory depression,but they have defects such as short duration of action and insufficient specificity.The devel-opment of novel stimulants targeting μ-opioid receptor agonists and the D-serine release pathway of astrocytes,as well as broad-spectrum antidotes based on"molecular cage"technology,has become a new sphere of research that aims at precisely reversing respiratory depression while preserving analgesic and sedative effects.This article reviews the biological mechanisms of respiratory depression caused by sedative hypnotic anesthetic drugs,explores the advantages and disadvantages of treatments currently availabe,and proposes new strategies for improving respiratory depression in the future.
