Author(s): Yu SM, Ko FN, Wu TS, Lee JY, Teng CM
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Abstract The pharmacological activity of cinnamophilin ((8R,8'S)-4,4'-dihydroxy-3,3'-dimethoxy-7-oxo-8,8'-neolignan), isolated from Cinnamomum philippinense, was studied in isolated rat aorta, guinea-pig trachea and rabbit platelets. Cinnamophilin was found to be a thromboxane A2 receptor blocking agent in these tissues as revealed by its competitive antagonism of the U-46619 (9,11-dideoxymethanoepoxy-9 alpha,11 alpha-prostaglandin F2 alpha)-induced contraction of rat aorta and guinea-pig trachea and aggregation of rabbit platelets with pA2 values of 7.3 +/- 0.2, 5.2 +/- 0.1 and 6.3 +/- 0.3, respectively. Protection against the irreversible vasoconstriction of rat aorta caused by U-46619 (0.05 microM) was obtained by cinnamophilin (10 microM) but not by caffeine (25 mM). Cinnamophilin (1-15 microM) also possessed voltage-dependent Ca2+ channel blocking action, judging from its antagonism of the high K+ (60 mM)- and Bay K 8644 (0.1 microM)-induced contraction in rat thoracic aorta. Cinnamophilin (30 microM) produced a slight relaxation of noradrenaline (3 microM)-induced tonic contractions, and this relaxing effect was abolished in the presence of nifedipine (1 microM). Nifedipine (10 microM) sufficient to inhibit high K(+)-induced contractions failed to attenuate the contractile response to U-46619. A high concentration of cinnamophilin (100 microM) did not affect the aortic contraction induced by endothelin-1, angiotensin II, carbachol or serotonin. Neither cAMP nor cGMP in rat aorta was increased by cinnamophilin. These results indicate that cinnamophilin is a selective thromboxane A2 receptor antagonist especially in rat aorta, and also possesses voltage-dependent Ca2+ channel blocking properties.
This article was published in Eur J Pharmacol
and referenced in Pharmaceutica Analytica Acta