The spasmolytic effects of an acqueous extract of cedrón (AEC) were studied on rat isolated duodenums. This plant (Aloysia citriodora Palau, Verbenaceae) is widely used for gastrointestinal disorders and as eupeptic in South America. AEC non-competitively inhibited the dose-response curve (DRC) of Ach (IC50 of 1.34 +/- 0.49 mg lyophilized/mL) and the DRC of Ca(2+) in high-[K(2-)](o) (IC50 of 2.64 +/- 0.23 mg/mL). AEC potentiated the non-competitive inhibition of either 30 micromol/L W-7 (a calmodulin blocker) and 5-15 micromol/L papaverine on the Ca(2+)-DRC. Also, AEC relaxed the contracture produced by high-[K(+)](o) (IC50 of 2.6 +/- 0.2 mg/mL) until 81.0 +/- 3.2% of the maximal effect of papaverine and 78.1+/- 5.0% of the quercetin, the most selective inhibitor of PDE. The AEC relaxation was non-competitively inhibited by 10-30 micromol/L methylene blue and competitively antagonized by 40 mmol/L TEA. The relaxation of 1mg/mL AEC was inhibited by hypoxia, but not that of 2mg/mL. Two flavonoids were identified by HPLC in the AEC: vitexin and isovitexin. Vitexin non-competitively inhibited the Ach-DRC (pD(2') of 5.7 +/- 0.4) but significantly run leftward the DRC of Ca(2+). Isovitexin did not significantly inhibit the DRC of Ach nor Ca(2+). The results suggest that the spasmolytic effect of AEC could be mostly associated to the increase in cGMP (target shared with the PDE inhibitors) and the activation of K(+)-channels. At low concentrations, AEC also inhibits the aerobic metabolism. The flavonoid vitexin is partially responsible for the effect, since it non-competitively inhibits Ach but not the Ca(2+) influx. Isovitexin was devoid of activity on duodenums.