[Substituted picolinic acids as DBH inhibitors. Inhibition of dopamine beta-hydroxylase and antihypertensive action].

The authors determined the dissociation constant, the constant of copper complex formation, the inhibitory action on the catecholamine biosynthesis enzyme dopamine beta-hydroxylase (DBH; copper glycoprotein), as well as the antihypertensive effect on spontaneously hypertensive rats of a series of substituted picolinic or fusaric acids (FA; 5-n-butylpicolinic acids). The substances investigated may be characterized as weak to medium-strong acids which form stable copper(II) complexes in solution and in the solid state. The concentrations required for a 50% inhibition of DBH range between 10(-6) and 10(-5) mol/l. The picolinic acid structure is of greater importance to enzyme inhibition than the butylpyridine structure. From the inhibition type of FA it may be deduced that the mechanism of inhibition cannot be explained only by the complex formation of the enzyme copper. Most of these derivatives are of hypotensive activity; some others exert a hypertensive effect. A quantitative correlation between the action on blood pressure and the enzyme inhibition cannot be established without calculation (quantitative structure-activity analysis). The hypotensive activity is above all due to DBH inhibition in the angiovascular region and in the suprarenal gland.