Flopropione (Flo) has been used for urolithiasis and gallstone as an anticonvulsant almost exclusively in Japan.  According to the package insert, its main mechanism of action is COMT inhibition, and this mechanism, as described in many pharmacology textbooks, frequently occurs in questions in state examinations for pharmacists.  As this mechanism is contrary to pharmacological common sense, i.e., ureter is contracted by adrenergic α stimulation and physiological relaxant of Oddi sphincter (OS) is not adrenergic, we confirmed this by experiment. The ureter was taken from male Guinea pig and its isometric contraction was recorded. Noradrenaline (NA) elicited periodical spike contractions. Flo (30 to 100 μM) reduced both its contractile force and frequency, whereas entacapone (Ent, 10 μM), whose inhibitory effect on COMT is much more potent than Flo, did not show any effect.  Isolated OS was perfused with nutrient solution 1 ml/hr, and its perfusion pressure was recorded. The OS preparation showed periodical increase in pressure without stimulants. Flo inhibited the spontaneous increase, whereas Ent did not show any effect. NA inhibited the pressure increase and its inhibition was blocked by α and β antagonists, whereas the inhibitory effect of Flo was not affected by the antagonists. These observations strongly indicate that there is no room for COMT inhibition in the mechanism of anticonvulsant effect of Flo. The true mechanism of smooth muscle relaxation by Flo is presently under investigation.