Effect of reduced barometric pressure on drug action and metabolism in mice

Abstract

Mice kept at a simulated altitude of 18,000 ft for 5 days had a shorter duration of loss of righting reflex with hexobarbital, zoxazolamine and mephenesin, but not with pentobarbital. Exposure to reduced pressure did not alter brain receptor sensitivity to these drugs. Decreased hexobarbital sleeping time was produced 3 days after initial simulated altitude exposure and was reversed within 3 days after return to normobaric conditions. The hepatic microsomal metabolism of aniline, hexobarbital, nitroanisole and dichlorophenolindophenol was increased in mice kept in a hypobaric chamber while that of methylaniline was not altered. Mice exposed to reduced pressure had a loss of total body weight, liver weight, and liver water content. Hepatic RNA-P and DNA content was increased, but there was no change in the hepatic microsomal protein or cytochrome P-450 content. A decreased hexobarbital sleeping time in different mice strains was observed at a simulated altitude of 18,000 ft but not at 8000 ft. The results suggest that the alterations in drug action observed may be due primarily to increased drug metabolism produced by hypobaric hypoxia.