[The hypotensive effect of aromatic amidines and imidazolines]

Some amidine, diamidine and diimidazoline derivatives were tested on their ability to lower the blood pressure of the rat. Except for 5-amidino-2-phenylindole (271/179) all substances led to a short-lasting hypotension, the dose relationship of some of which was investigated. The biscationic character was a prerequisite for a strong hypotensive action. The predominantly peripheral origin of the blood pressure lowering action was shown for the substances pentamidine, diminazene, 6-amidino-2- (4-amidinophenyl)-indole (102/198), 5-amidino-2-(4-amidinophenyl) - benzofurane (150/49) and 2,6-diamidinoindole (261/115). A parasympathomimetic and histaminic efficiency could be excluded. The pressor effect of norepinephrine (noradrenaline) was reduced under the influence of pentamidine, diminacene and 102/198. With the dog 102/198 and 261/115 showed a diminution of heart rate and force as well as a vasodilatory effect. Using the rat, different cardiovascular parameters behaved analogous. Pentamidine, diminazene, 102/198 and 261/115 increased the force of contraction of the isolated rat atrium. Toxic effects were observed in doses as high as 0,5 mmol/l and l mmol/l. Pentamidine reduced the heart rate of the isolated atrium in a dose-dependent manner. Taking into account the in vitro results, the heart effects were interpreted as being reflectory. In the isolated rat aorta preparation the aforementioned substances in low doses shifted the dose-response curves of norepinephrine to the right, whereas higher doses also reduced the maximum contraction. Considering the results on the intact animal, a direct action of the diamidines on vascular smooth muscle was discussed.