A modern literature review of carbon monoxide poisoning theories, therapies, and potential targets for therapy advancement

Toxicology. 2015 Aug 6;334:45-58. doi: 10.1016/j.tox.2015.05.004. Epub 2015 May 18.


The first descriptions of carbon monoxide (CO) and its toxic nature appeared in the literature over 100 years ago in separate publications by Drs. Douglas and Haldane. Both men ascribed the deleterious effects of this newly discovered gas to its strong interaction with hemoglobin. Since then the adverse sequelae of CO poisoning has been almost universally attributed to hypoxic injury secondary to CO occupation of oxygen binding sites on hemoglobin. Despite a mounting body of literature suggesting other mechanisms of injury, this pathophysiology and its associated oxygen centric therapies persists. This review attempts to elucidate the remarkably complex nature of CO as a gasotransmitter. While CO's affinity for hemoglobin remains undisputed, new research suggests that its role in nitric oxide release, reactive oxygen species formation, and its direct action on ion channels is much more significant. In the course of understanding the multifaceted character of this simple molecule it becomes apparent that current oxygen based therapies meant to displace CO from hemoglobin may be insufficient and possibly harmful. Approaching CO as a complex gasotransmitter will help guide understanding of the complex and poorly understood sequelae and illuminate potentials for new treatment modalities.

Keywords: Carbon monoxide poisoning; Cardiac ion channels; Gasotransmitter; Neuronal ion channels; Nitric oxide; Reactive oxygen species.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidotes / therapeutic use*
  • Carbon Dioxide / blood
  • Carbon Dioxide / toxicity*
  • Carbon Monoxide Poisoning / blood
  • Carbon Monoxide Poisoning / physiopathology
  • Carbon Monoxide Poisoning / therapy*
  • Carboxyhemoglobin / metabolism
  • Gases
  • Humans
  • Hyperbaric Oxygenation*
  • Ion Channels / drug effects
  • Ion Channels / metabolism
  • Molecular Targeted Therapy
  • Nitric Oxide / metabolism
  • Reactive Oxygen Species / metabolism
  • Signal Transduction / drug effects
  • Treatment Outcome


  • Antidotes
  • Gases
  • Ion Channels
  • Reactive Oxygen Species
  • Carbon Dioxide
  • Nitric Oxide
  • Carboxyhemoglobin