CINNAMOPHILIN, A NOVEL THROMBOXANE A(2) RECEPTOR ANTAGONIST, ISOLATEDFROM CINNAMOMUM PHILIPPINENSE

The pharmacological activity of cinnamophilin 4'-dihydroxy-3,3'-dimeth oxy-7-oxo-8,8'-neolignan), isolated from Cinnamomum philippinense, was studied in isolated rat aorta, guinea-pig trachea and rabbit platelet s. Cinnamophilin was found to be a thromboxane A(2) receptor blocking agent in these tissues as revealed by its competitive antagonism of th e U-46619 (9,11-dideoxymethanoepoxy-9 alpha,11 alpha-prostaglandin F-2 alpha)-induced contraction of rat aorta and guinea-pig trachea and ag gregation of rabbit platelets with pA(2) values of 7.3 +/- 0.2, 5.2 +/ - 0.1 and 6.3 +/- 0.3, respectively. Protection against the irreversib le vasoconstriction of rat aorta caused by U-46619 (0.05 mu M) was obt ained by cinnamophilin (10 mu M) but not by caffeine (25 mM). Cinnamop hilin (1-15 mu M) also possessed voltage-dependent Ca2+ channel blocki ng action, judging from its antagonism of the high K+ (60 mM)- and Bay K 8644 (0.1 mu M)-induced contraction in rat thoracic aorta. Cinnamop hilin (30 mu M) produced a slight relaxation of noradrenaline (3 mu M) -induced tonic contractions, and this relaxing effect was abolished in the presence of nifedipine (1 mu M). Nifedipine (10 mu M) sufficient to inhibit high K+-induced contractions failed to attenuate the contra ctile response to U-46619. A high concentration of cinnamophilin (100 mu M) did not affect the aortic contraction induced by endothelin-1, a ngiotensin II, carbachol or serotonin. Neither cAMP nor cGMP in rat ao rta was increased by cinnamophilin. These results indicate that cinnam ophilin is a selective thromboxane A(2) receptor antagonist especially in rat aorta, and also possesses voltage-dependent Ca2+ channel block ing properties.