Comparative investigation of inhibitors of extracerebral dopa decarboxylase in man and rats

The decarboxylase inhibitor Ro 4–4602 N¹-(dl -seryl)-N²-(2,3,4-trihydroxybenzyl)hydrazine] in doses of 3.4–34.0 μmol/kg (1–10mg/kg) progressively enhances the increase of dopa and 3-O-methyldopa and diminishes the rise of phenolcarboxylic acids in human plasma induced by administration of l -dopa. A dose of 3.4 μmol/kg Ro 4–4602 is approximately equipotent to 17.0 μmol/kg MK 485 β-(3,4-dihydroxyphenyl)-α-hydrazino-α-methyl-dl -propionie acid]. Ro 4–4602, combined with 2 mg/kg l -dopa, causes a higher increase of catecholamines than 20 mg/kg l -dopa alone in the striatum and probably in the hypothalamus of rat brain, whereas in the other brain areas the amine rise is equal after both treatments. MK 485 in doses equimolar to Ro 4–4602 has a less marked effect in all brain areas. Either inhibitor (10–2 μmol/kg) combined with 2 mg/kg l -dopa causes markedly less increase of catecholamines than 20 mg/kg l -dopa alone in the rat heart. Ro 4–4602, in small single doses, used at present in the treatment of Parkinson's syndrome, markedly inhibits the extracerebral decarboxylation of l -dopa in man and rats and is more potent than MK 485.