RELATION OF BRAIN SENSITIVITY AND HEPATIC METABOLISM OF HEXOBARBITONE TO DOES-RESPONSE RELATIONS IN INFANT AND YOUNG RATS

The dose‐response relation to hexobarbitone of infant (5 day) and young (44 day) male rats was examined, and the relative contribution of hepatic metabolism (measured in vitro) and changes in brain sensitivity to the overall response were evaluated. The infant rat shows a parallel shift to the left in its dose‐response curve with the relative potency of hexobarbitone almost 5 times greater than for the 44 day old animal. The slope of the curves show marked changes at the first lethal dose level of drug. This and other evidence suggest that death may not be merely an extension of the mechanism causing hypnosis. Infant rats exhibited a shorter increment in sleep time for increasing doses of hexobarbitone than is predictable from their low rate of in vitro metabolism. Although this is also true for the young rats, the two values are in much closer agreement than for the infant animals. Brain concentrations of hexobarbitone, measured upon regaining of the righting reflex, were lower in the infant than in the young rat. This suggests the central nervous system of the infant rat has an increased sensitivity to the drug. 1969 Royal Pharmaceutical Society of Great Britain