Catecholamines

Rats anesthetized with halothane or cyclopropane have unaltered norepinephrine concentrations in most brain regions but may have an elevated norepinephrine content in the nucleus accumbens, locus ceruleus, and central gray catecholamine areas.^[56] Although anesthesia does not deplete brain norepinephrine, a change in norepinephrine availability significantly influences anesthetic requirement. Drugs that decrease central levels of norepinephrine result in a dose-related decrease in the halothane MAC, whereas drugs that elevate central norepinephrine levels increase the anesthetic requirement.^[57]

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In contrast to those of norepinephrine, central levels of dopamine appear to be inversely related to anesthetic requirement. Administration of levodopa to mice increases striatal dopamine content and decreases the halothane MAC,^[58] and an increase in striatal dopamine content is associated with halothane anesthesia. ^[59] Conversely, chemical destruction of dopaminergic neurons lowers dopamine content and increases the halothane MAC.^[58]

The administration of α₂ -adrenergic agonists markedly lowers inhaled anesthetic requirement in animals and humans. Dexmedetomidine, an agonist that is more selective than clonidine for the α₂ -adrenoreceptor, produces a remarkable decrease in the halothane^[60] MAC in dogs to less than 10% of the control value ( Fig. 4-8 ). This effect appears to be highly specific for the α₂ -adrenoreceptor, because the optical isomer L-medetomidine does not alter MAC (see Fig. 4-8 ). The ability of spinally administered α₂ -adrenoreceptor antagonists to block the antinociceptive effects of nitrous oxide and isoflurane also suggests an adrenergic mechanism for the analgesic actions of inhaled anesthetics.^[61]