signals locally. General anesthetics are potent sedative-hypnotics
administered during surgical procedures. They act in the brain to
reduce overall CNS neural activity, producing a loss of consciousness
and thus lack of awareness of any sensory experience, including pain.
They tend to be easily volatilized liquids that can be delivered to the
patient by inhalation, allowing for rapid onset of effects and quick re-
sponses to adjustments in dose.
The first general anesthetic to be used in medicine was ethanol:
the patient would be given whiskey to drink before surgery was per-
formed. In the mid-nineteenth century, diethyl ether was introduced
as a surgical anesthetic; it was more potent than alcohol and more
volatile, and thus readily administered by inhalation. Used for more
than a century, diethyl ether was replaced in the mid-twentieth cen-
tury by various other volatile chemicals.
H H H H F Br F3C oO F
14 1 ot 1 ° —
H-C—-C—O—-C-C—-H F=-C-2-
1 | 1 if CF,
HH H H F Cl Sevoflurane
Diethyl ether HalothaneMost of these new molecules were derived from small hydrocarbons
and ethers by replacing one or more of the hydrogen atoms with halo-
gen atoms, such as bromine, chlorine, or fluorine. The first to be intro-
duced was halothane, in the 1950s. Currently used inhalation general
anesthetics include desflurane and sevoflurane.
These diverse sedative-hypnotic drugs are all thought to have sim-
ilar primary neurochemical mechanisms of action in the brain. They
all act at ionotropic GABA receptors, facilitating the action of GABA at
the receptor. This increases inhibition in the CNS by increasing GABA-
induced CI flow into cells. This is believed to in some way give rise to