Endogenous anesthetic

Carbon dioxide (CO₂) is an abundant gas produced as the final product of glucose metabolism in animals. CO₂ anesthesia is most frequently used for anesthetizing flies. {{cite journal |last1=Nilson |first1=Theresa L. |last2=Sinclair |first2=Brent J. |last3=Roberts |first3=Stephen P. |title=The effects of carbon dioxide anesthesia and anoxia on rapid cold-hardening and chill coma recovery in Drosophila melanogaster |journal=Journal of Insect Physiology |date=October 2006 |volume=52 |issue=10 |pages=1027–1033 |doi=10.1016/j.jinsphys.2006.07.001|pmc=2048540 }} But it has also been considered as a fast acting anesthetic in small laboratory animals and in humans.{{cite journal |last1=Hansen |first1=SB |title=Mechanisms of General Anesthesia. |journal=Annual review of biochemistry |date=1 April 2025 |doi=10.1146/annurev-biochem-030222-121430 |pmid=40169006}}{{cite journal |last1=Kohler |first1=I. |last2=Meier |first2=R. |last3=Busato |first3=A |last4=Neiger-Aeschbacher |first4=G. |last5=Schatzmann |first5=U. |title=Is carbon dioxide (CO₂) a useful short acting anaesthetic for small laboratory animals? |journal=Laboratory Animals |date=1 April 1999 |volume=33 |issue=2 |pages=155–161 |doi=10.1258/002367799780578390}}

In the 1900s, CO₂ anesthesia, known as CO₂ therapy was used by psychiatrists for the treatment of anxiety. The patients would receive 70% CO₂ in combination with 30% oxygen causing rapid and reversible loss of continuousness.{{cite journal |last1=LAVERNE |first1=AA |title=Rapid coma technique of carbon dioxide inhalation therapy. |journal=Diseases of the nervous system |date=May 1953 |volume=14 |issue=5 |pages=141–4 |pmid=13052042}}

Ammonia has also been shown to have anesthetic properties.{{cite journal |last1=Brosnan |first1=Robert J. |last2=Yang |first2=Liya |last3=Milutinovic |first3=Pavle S. |last4=Zhao |first4=Jing |last5=Laster |first5=Michael J. |last6=Eger |first6=Edmond I. |last7=Sonner |first7=James M. |title=Ammonia Has Anesthetic Properties |journal=Anesthesia & Analgesia |date=June 2007 |volume=104 |issue=6 |pages=1430–1433 |doi=10.1213/01.ane.0000264072.97705.0f|doi-access=free }} It is released during protein catabolism, and its presence reduced the requirement for inhaled anesthetics. Whether the endogenous release of the ammonia is contributing to an anesethetic effect in vivo has not yet been established.

The most abundant endogenous anesthetics are small hydrophobic gaseous metabolites of catabolism and likely work through a membrane-mediated mechanism of general anesthesia.

In the 1800s anoxia was considered the mechanism of CO₂ anesthesia.{{cite journal |last1=Antiquack |title=Surgical Humbug |journal=The Lancet |date=1826 |volume=5 |issue=127 |page=646}} However, studies in humans showed the opposite, oxygenation of the brain tissue increases with increase CO₂ in the lung.{{cite journal |last1=Moriarty |first1=John D. |title=EVALUATION OF CARBON DIOXIDE INHALATION THERAPY |journal=American Journal of Psychiatry |date=April 1954 |volume=110 |issue=10 |pages=765–769 |doi=10.1176/ajp.110.10.765}} More recent studies have shown in bees that anoxia is also not the mechanism.{{cite journal |last1=Cressman |first1=Anna |last2=Amsalem |first2=Etya |title=Impacts and mechanisms of CO₂ narcosis in bumble bees: narcosis depends on dose, caste and mating status and is not induced by anoxia |journal=Journal of Experimental Biology |date=1 January 2023 |volume=226 |issue=1 |doi=10.1242/jeb.244746|doi-access=free }}

In humans, CO₂ raises the threshold of stimulation of the nerve cell, decreases the speed of conduction of impulses along the nerve, and increases the height and prolonged duration of the action potential.{{cite journal |last1=Moriarty |first1=John D. |title=EVALUATION OF CARBON DIOXIDE INHALATION THERAPY |journal=American Journal of Psychiatry |date=April 1954 |volume=110 |issue=10 |pages=765–769 |doi=10.1176/ajp.110.10.765}}

While the endogenous anesthetics appear to have a similar mechanism of action to inhaled anesthetics, their rapid endogenous metabolism complicates their use in humans. Apart from flies, exogenous compounds have proven more useful for maintaining general anesthesia.

The first private demonstration of an anesthetic was carbon dioxide by Henry Hill Hickman in a dog cerca 1823.

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Category:Anesthesia