In Vitro Effects of the New Calcium Antagonist Lacidipine

Abstract

Stimulatory effects of HSR-803 on intestinal motor activity in vitro were studied in guinea pig ileum. HSR-803 (1 x 10(-6)-1 x 10(-4) M) increased the amplitude of longitudinal muscle contractions and increased the frequency of peristalsis in isolated segments of guinea pig ileum. The stimulatory effect in amplitude and not frequency was abolished by 1 x 10(-6) M atropine. In the Magnus method with ileal segments, HSR-803 (1 x 10(-7) - 1 x 10(-4) M) produced contractions concentration-dependently, which were inhibited by atropine (1 x 10(-8) and 3 x 10(-8) M) and 3 x 10(-7) M tetrodotoxin (TTX). In the [3H]-quinuclidinyl benzilate (QNB) binding experiment with ileal smooth muscle, HSR-803 had low affinity for acetylcholine (ACh) receptors (pKi = 4.47 +/- 0.04). In addition, HSR-803 failed to increase the spontaneous release and the electrical stimulation-induced [3H]ACh release in ileal smooth muscle. On the other hand, HSR-803 (1 x 10(-5) M) enhanced contractions induced by ACh, but had no effect on contractions induced by carbachol, which is not hydrolyzed by acetylcholinesterase (AChE). In conclusion, HSR-803 stimulated ileal motor activity. However, HSR-803 had low affinity for ACh receptors and had no influence on ACh release. It is likely that HSR-803 stimulated motor activity mainly due to prevention of ACh hydrolysis.