Endogenous anesthetic

Endogenous anesthetics are analogs of anesthetics the body makes that have the properties and similar mode of action of general anesthetics.

Carbon dioxide
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. But it has also been considered as a fast acting anesthetic in small laboratory animals.

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.

Ammonia
Ammonia has also been shown to have anesthetic properties.

Mechanism of action
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. However, studies in humans showed the opposite, oxygenation of the brain tissue increases with increase CO2 in the lung. More recent studies have shown in bees that anoxia is also not the mechanism.

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.

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.

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