2,4-Diamino-6-hydroxypyrimidine specifically inhibits GTP cyclohydrolase I, which is crucial in the initial step of pterin synthesis. It impedes the formation of Tetrahydrobiopterin (BH4) and consequently reduces the production of nitric oxide (NO)[1][2]. 2,4-Diamino-6-hydroxypyrimidine, also known as DAHP, demonstrates a dose-related decrease in nitric oxide (NO) levels in chicken peritoneal macrophages (PECs) and the avian MC29 virus-transformed macrophage cell line, HD11[1]. Treatment with 2,4-Diamino-6-hydroxypyrimidine (DAHP; at a concentration of 5 mM for 24 hours) notably decreases levels of both BH4 and VCAM-1 over time in HUVEC cells. The synthesis of VCAM-1 and GTPCH proteins is reduced by 2,4-Diamino-6-hydroxypyrimidine, which is partially due to the suppression of NF-κB within the nucleus of HUVEC[2].
2,4-Diamino-6-hydroxypyrimidine 动物研究
Animal study
Upon administering 2,4-Diamino-6-hydroxypyrimidine at a dosage of 3 g/kg/day for four days in mice, there was a reduction in serotonin levels in the duodenum and colon to about 46% and 40% of control values, respectively. 2,4-Diamino-6-hydroxypyrimidine led to a swift decline (with a half-life of under 12 hours) in BH4 concentrations across all tested tissues except the brain. The BH4 levels normalized within less than 24 hours after stopping the administration of 2,4-Diamino-6-hydroxypyrimidine[3].
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