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

DOI Web Site PubMed 3 Citations
  • NAGAI Yasuo
    Central Research Division, Takeda Chemical Industries, Ltd.
  • NARUMI Shigehiko
    Central Research Division, Takeda Chemical Industries, Ltd.
  • SAJI Yoshiaki
    Central Research Division, Takeda Chemical Industries, Ltd.
  • NAGAWA Yuji
    Central Research Division, Takeda Chemical Industries, Ltd.

Bibliographic Information

Other Title
  • ＴＲＨ類縁体（ＤＮ‐１４１７）　　静脈内投与後のラットにおける血中濃度および脳内分布
  • TRH ルイエンタイ DN-1417 ジョウミャクナイ トウヨゴ ノ ラット
  • Blood level and brain distribution determined by radioimmunoassay after intravenous administration in rats

Search this article

Description

Thyrotropin-releasing hormone (TRH) and its analog, DN-1417 (γ-butyrolactone-γ-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 α- and β-phase were 3 ?? 7 and 15 ?? 22 min, respectively. The half-life of the blood level of immunoreactive-DN-1417 was 2 ?? 3 times longer than that of TRH. As a result, the area under the curve of DN-1417 was 2.5 ?? 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 ?? 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.

Journal

Citations (3)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top