Tolerance Studies
The inhaled anesthetic requirement can be increased by chronic
exposure of mice to subanesthetic levels of nitrous oxide.[160]
The maximal increase in the nitrous oxide righting-reflex ED50
for mice
placed under 40% to 70% nitrous oxide is approximately 0.25 atm and occurs after
2 weeks of continuous exposure.[160]
[161]
No significant differences in membrane order or in the composition of purified synaptic
membrane fatty acid, phospholipid, or cholesterol occur in mice tolerant to nitrous
oxide.[160]
[161]
Prolonged exposure of rats to nitrous oxide decreases brainstem opiate receptor
density by approximately 20% and may in part account for the tolerance to the analgesic
action of nitrous oxide.[162]
In humans, an acute tolerance to the analgesic effect of nitrous
oxide is seen in some patients within 10 to 60 minutes of administration.[163]
A rapidly developing tolerance to gaseous agents is also seen in rodents.[164]
[165]
The mechanistic bases of this acute tolerance
remain to be determined.
