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Distribution and metabolism of l ‐3‐O‐methyldopa in rats
Author(s) -
BARTHOLINI G.,
KURUMA I.,
PLETSCHER A.
Publication year - 1970
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1970.tb10627.x
Subject(s) - methyldopa , metabolism , homovanillic acid , endocrinology , chemistry , kidney , medicine , urine , biochemistry , biology , blood pressure , receptor , serotonin
1 . After intraperitoneal administration of l ‐2 −14 C‐3‐O‐methyldopa ( 14 C‐O‐methyldopa) to rats, the amino‐acid was distributed evenly in blood, brain, heart, adipose tissue and liver, whereas it accumulated more in the kidney and the pancreas. 14 C‐O‐methyldopa showed a biological half‐life of about 12–13 h in blood, brain and heart. 2 . The concentration curve of 14 C‐O‐methyldopa in brain (after increasing doses of the amino‐acid) was linear if measured 2 h after administration, but seemed to reach a plateau at the higher doses if determined after 16 h. 3 . The concentrations of 14 C‐O‐methyldopa metabolites (mainly homovanillic acid and 4‐hydroxy‐3‐methoxyphenyllactic acid) were low, except in the kidney, and varied according to the tissue. 4 . Twenty‐four hours after administration of 14 C‐O‐methyldopa, 33% of the injected radioactivity appeared in the urine. This radioactivity consisted of about 95% of metabolites (probably in the main 14 C‐homovanillic acid and 14 C‐4‐hydroxy‐3‐methoxyphenyllactic acid) and of 5% of unchanged 14 C‐O‐methyldopa. In the faeces, 10% of the radioactivity appeared, mainly as metabolic end‐products. 5 . It is concluded that 14 C‐O‐methyldopa easily penetrates from the blood into various tissues, including brain, and that the majority of the amino‐acid undergoes a slow metabolism. The different shape of the concentration curves for 14 C‐O‐methyldopa in the brain after 2 and 16 h might indicate the presence of two tissue pools of the amino‐acid.