[A TRH analog (DN-1417). Blood level and brain distribution determined by radioimmunoassay after intravenous administration in rats].

Thyrotropin-releasing hormone (TRH) and its analog, DN-1417 (gamma-butyrolactone-gamma-carbonyl-L-histidyl-L-prolinamide citrate), were administered intravenously to rats, and the blood level and brain distribution were determined by a specific radioimmunoassay. Degradation half-life of DN-1417 in the brain homogenate and blood was 27.5 min and those of TRH were 5 and 7.5 min, respectively. After the administration of DN-1417 (0.625, 2.5 and 10 mg/kg), the blood levels of immunoreactive-DN-1417 exhibited an apparent two compartment open model. The half-life values of the alpha- and beta-phase were 3 approximately 7 and 15 approximately 22 min, respectively. The half-life of the blood level of immunoreactive-DN-1417 was 2 approximately 3 times longer than that of TRH. As a result, the area under the curve of DN-1417 was 2.5 approximately 6 times larger than that of TRH. Blood level of immunoreactive-2-hydroxy-4-carboxybutyryl-histidyl-prolinamide+ ++ (DN-COOH), a main metabolite of DN-1417, was not more than 1% of the immunoreactive DN-1417 level. The distribution of DN-1417 into whole brain was attained its peak at 1 approximately 2 min after the administration. The percentage of transported DN-1417 into the brain at peak time was 0.062-0.163% of each of the doses administered. After the administration of DN-1417 (2.5 mg/kg), the pituitary, nucleus accumbens and hypothalamus showed higher concentrations, while the striatum showed the lowest concentration in the brain tissue examined.