Lithium塩の1回および反復投与時の動態と行動薬理学的研究

Abstract

Absorption, distribution and excretion after oral administration of lithium carbonate (Li2CO3) and/or lithium chloride (LiCl) were studied in Wistar rats and beagle dogs. The maximum level of concentration in the blood was seen within 4 hr after administration of Li2CO3, and a greater part of the orally dosed Li2CO3 was excreted into the urine. The blood and urine Li levels after the administration of LiCl were similar to those seen with Li2CO3. In dogs, Li2CO3 was more slowly excreted into the urine than it was in rats. Li was selectively incorporated into the thyroid and pituitary a short time after administration, and was not detected in any organ 7 days after cessation of repeated dosing for 19 days. The movement of Li into the brain was slow and relatively low levels were achieved after a single administration, but high and constant levels were shown after repeated administration. Effects of Li salts on behavior of ddy mice with repeated administration were investigated. The spontaneous motor activity was suppressed with Li2CO3 more strongly than with LiCl. The high dose of Li2CO3 suppressed not only the stimulating actions of methamphetamine and cocaine, but the ptotic and hypothermic action of reserpine. From these results, it is concluded that the repeated administration of Li salts reveals higher levels of Li ion in the brain than does a single administration, and also more responsive action on the central nervous system.