Distribution and metabolism of l‐3‐O‐methyldopa in rats

Abstract

1 . After intraperitoneal administration of l-2⁻¹⁴C-3-O-methyldopa (¹⁴C-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. ¹⁴C-O-methyldopa showed a biological half-life of about 12–13 h in blood, brain and heart. 2 . The concentration curve of ¹⁴C-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 ¹⁴C-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 ¹⁴C-O-methyldopa, 33% of the injected radioactivity appeared in the urine. This radioactivity consisted of about 95% of metabolites (probably in the main ¹⁴C-homovanillic acid and ¹⁴C-4-hydroxy-3-methoxyphenyllactic acid) and of 5% of unchanged ¹⁴C-O-methyldopa. In the faeces, 10% of the radioactivity appeared, mainly as metabolic end-products. 5 . It is concluded that ¹⁴C-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 ¹⁴C-O-methyldopa in the brain after 2 and 16 h might indicate the presence of two tissue pools of the amino-acid.