A COMPARISON OF THE ABSORPTION, DISTRIBUTION AND METABOLISM OF RESERPINE IN INFANT AND ADULT RATS

¹ Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota

The absorption, distribution and metabolism of tritiated reserpine (H²-reserpine) were studied in infant (11 days old) and adult rats in an attempt to assess the possible role of each in determining the greater degree of brain norepinephrine (NE) depletion produced by reserpine in infants than adults. After i.p. or s.c. administration of H²-reserpine (0.1 mg/kg) the concentration of reserpine in brain was greater in infant than adult animals at all times studied (20 min-18 hr). The mean concentration 20 min after administration was higher after s.c. than i.p. administration at both ages. Estimation of H²-reserpine concentrations in pooled samples of plasma 20 min after administration of the drug revealed that concentrations in the infant were 6- to 7-fold greater, and plasma/brain concentration ratios were 2-fold greater than corresponding adult values. The rate of disappearance of H²-reserpine from subcutaneous tissue in the hind limb of infants was not significantly different from that of adults. A larger percentage of the administered dose of H²-reserpine was recovered from infant than from adult carcasses 20 min after administration. The Michaelis constant for the hydrolysis of the trimethoxybenzoyl ester bond of reserpine by enzymes in the liver of the infant rat was not significantly different from that of adult preparations, but the maximal velocity of infants was significantly below that of adults. It is concluded that the greater depletion of NE in infant than in adult rat brain after a given dose of reserpine may be the result of a lesser capacity of the infant rat to metabolize reserpine. This could account for the higher plasma and tissue levels of reserpine observed in infants. These findings do not exclude the possibility of a greater sensitivity of infant brain NE storage sites to the depleting action of reserpine as another cause for the difference between adults and infants.