Effects of methyl O-(4-hydroxy3-methoxycinnamoyl)reserpate (CD-3400) on the smooth muscle preparations

Abstract

Effects of methyl O-(4-hydroxy-3-methoxycinnamoyl)reserpate (CD-3400), a new antihypertensive agent, on the peripheral nervous system in mice, rats and guinea pigs were investigated and compared with effects of reserpine and rescinnamine. Oral administration of CD-3400 in doses from 40 to 320 mg/kg revealed a miotic action and such was weaker than that seen with reserpine and rescinnamine. The intestinal propulsion in mice was accelerated by pretreatment with reserpine, but no so with CD-3400. In isolated guinea pig vas deferens, CD-3400 at a concentration of 1 × 10^-5M inhibited on norepinephrine-induced contraction non-competitively. However, in isolated rat vas deferens pretreated with CD-3400 (1 mg/kg, i.p.) for 5 days, norepinephrine-induced contraction was potentiated and this effect was weaker than that seen with reserpine and rescinnamine. In isolated rat vas deferens pretreated with CD-3400 for 1, 2 and 5 days, the contraction induced by tyramine (3 × 10^-5M) was significantly inhibited. The effect was qualitively similar to those of reserpine and rescinnamine. The intravenous administration of these three rauwolfia alkaloids in doses of 1, 2 and 4 mg/kg had no effect on the spontaneous movement of rat uterus. In isolated rat uterus pretreated with CD-3400, no significant effect was observed on oxytocin and isoproterenol-induced responses. The peripheral actions of CD-3400 are attributed to a deterioration in the function of the sympathetic nerve resulting in depletion of catecholamine stores. Effects of CD-3400 were slightly weaker than those of reserpine and rescinnamine.