Abstract
3-Aminopropanesulfonic acid (homotaurine, HT) was proven to lower the blood pressure in laboratory animals, the hypotensive effect varying demonstrably among various animal species. We had also described in the previous report that chemical structures related to the hypotensive effect of several ω-aminosulfonic acids which are chemically related to HT. This time, we studied the effect on the smooth muscle, the diuretic action, and excretion in the urine of HT as well as histopathological examination of animals having received the compound, with the results as follows:
1) The motility of isolated rabbit intestine was scarcely affected by the presence of 10-3 g HT per ml in the bath fluid but was significantly suppressed in the presence of not less than 3×10-3 g per ml.
2) Contractile responses of isolated guinea-pig intestine produced with histamine, acetylcholine or 5-HT were inhibited by high concentrations of HT. However, the intestinal contraction with barium chloride was hardly affected by HT.
3) HT was observed to produce, when applied at high concentrations, enhancement of motility and elevation of tonus of isolated rat uterus. Inhibition of the uterine movement by adrenaline or noradrenaline was antagonized by pretreatment with HT. HT, however, failed to exert any appreciable effect upon contraction by acetylcholine.
4) Maximum doses of HT produced diuretic effects in mice and in rats.
5) From rabbits receiving single oral doses of 100 mg HT per kg, 20 to 30 per cent of the administered dose were recovered in the urine as unmodified HT compound.
6) When HT was administered orally at dosage level of 100 mg/kg daily to rabbits, a salient decrease or even complete disappearance of histidine in the basic amino acid pattern of the urine occurred from the second week after the start of oral administration onward whereas both the neutral and acid amino acid patterns of urine remained unchanged.
7) Histopathological examination of rabbits and rats which had received 100 mg of HT per kg of body weight daily for a long period of time revealed no significant adverse toxicologic findings whatsoever.
