RT Journal Article
SR Electronic
T1 PHARMACOLOGIC BASIS FOR THE INCREASED SENSITIVITY OF THE NEWBORN RAT TO MORPHINE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 105
OP 112
VO 141
IS 1
A1 Kupferberg, Harvey J.
A1 Way, E. Leong
YR 1963
UL http://jpet.aspetjournals.org/content/141/1/105.abstract
AB The toxicity of intraperitoneally injected morphine in newborn rats was determined and found to decrease with age. The greatest change occurred between the ages of 16 to 32 days; the LD50 for the 32-day-old rat was found to be nearly 4-fold that of the 16-day-old. Some differences in the ability to excrete and conjugate morphine in the 16- and the 32-day-old rat were noted but these variations were not directly correlated to toxicity. The brain levels of free morphine at various time intervals were found to be two to four times greater in 16-day-old rats than in the 32-day-old after equal doses based on weight. When equal toxic doses were given, maximum brain levels were approximately the same. It is concluded that the toxicity of morphine is related to brain concentrations and that the change in sensitivity to morphine with age can be correlated primarily with a change in permeability of the brain to morphine.