| Popis: |
The transfer, distribution and degradation of taltirelin in the brain were investigated after oral (3 mg/kg) or intravenous (1 mg/kg) administration and injection into cisterna cerebellomedullaris (300 μg/kg) in rats. 1. Taltirelin was hardly degraded for 3 hr in blood, whereas TRH was degraded with a half-life of 5.4 min. Taltirelin and TRH were degraded by the brain homogenate with half-lives of 64.4 and 7.9 min, respectively, suggesting that taltirelin is 8 times more stable than TRH in the brain. In the cerebrospinal fluid taltirelin and TRH were equally stable for 3 hr. 2. Concentration of unchanged taltirelin in the brain decreased more slowly with a half-lives of 55.4 ?? 65.7 min than that in the blood (t1/2 : 23.1 min) after intravenous administration of taltirelin. After oral administration, the brain concentrations of unchanged taltirelin reached the maximum levels of 135 ?? 364 pg/g and then decreased slowly. The unchanged taltirelin was not detected in the brain at 6 hr after dosing. 3. After injection of 14C-taltirelin into cisterna cerebellomedullaris, the brain concentrations of radioactivity reached the maximum levels of 2.3 ?? 5.5 μg eq./g at 1 hr after injection and then decreased slowly. These results indicated that taltirelin was transferred from cerebrospinal fluid into the brain, in which taltirelin was retained for a long time. 4. After intravenous adm inistration of 14C-taltirelin or 3H-TRH, there is a difference in the brain distribution of radioactivity between taltirelin and TRH. Radioactive concentration in pituitary gland, which was target organ of hormonic effect, at 5 min after intravenous administration of 14C-taltirelin was 1/10 of that after dosing of 3H-TRH. |
