Relative amnesic potency of five inhalational anesthetics follows the Meyer-Overton rule.
BACKGROUND
Doses of volatile anesthetics around 0.3 minimum alveolar concentration (MAC) inhibit learning. However, threshold amnesic doses and relative potencies between agents are not well established. The authors determined amnesic potency in rats for four common volatiles and nitrous oxide.


METHODS
After institutional review board approval, adult Sprague-Dawley rats received inhibitory avoidance training during exposure to either air or various subanesthetic doses of desflurane, sevoflurane, isoflurane, halothane, or nitrous oxide (4-21 rats/dose). Animals were trained to remain in a starting "safe" compartment for 100 consecutive seconds by administering a foot shock (0.3 mA) each time they entered an adjacent "shock" compartment. Memory was assessed at 24 h. Anesthetic effects on pain thresholds were separately determined.


RESULTS
Learning: Only relatively higher doses of sevoflurane, halothane, and desflurane increased the number of shocks required for task acquisition. Memory: Significantly decreased retention performance (P < 0.05) was found at relatively low inspired concentrations of 0.2% isoflurane, 0.3% sevoflurane and halothane, 0.44% desflurane, and 20% nitrous oxide. Amnesic potency was nitrous oxide >/= desflurane > sevoflurane >/= isoflurane >> halothane, (rank-ordered ED50 values as %MAC). Amnesic potency correlated with oil:gas partition coefficients (r = -0.956, P < 0.007). Halothane, only at 0.08%, enhanced retention (P < 0.01). All agents were analgesic at higher doses.


CONCLUSIONS
Amnesic potency differs between agents; nitrous oxide is most potent and halothane is least potent relative to MAC. The amnesic threshold ranges from 0.06 to 0.3 MAC. The correlation between potency and oil:gas partition coefficients suggests a fundamental role for hydrophobicity in mediating amnesia, similar to its association with MAC. Some agents (e.g., halothane) may enhance aversive memory retention at doses typically encountered during emergence.
Department of Anesthesiology, Center for the Nuerobiology of Learning and Memory, University of California-Irvine, Irvine, California, USA. malkire@uci.edu
Michael T
MT
Alkire
Lukasz A
LA
Gorski
D000647:Amnesia / Q000139:chemically induced*; D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D008297:Male; D008568:Memory / Q000187:drug effects; D009609:Nitrous Oxide / Q000494:pharmacology; D017288:Pain Threshold / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D011650:Pulmonary Alveoli / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D018685:Anesthetics, Inhalation; D009609:Nitrous Oxide