In this study, tetramethylpyrazine (TMPZ) was effective in reducing the mor
tality of ADP-induced acute pulmonary thromboembolism in mice when administ
ered intravenously at doses of 40 and 80 mug/g. In addition, intravenous in
jection of TMPZ (10 mug/g) significantly prolonged the bleeding time by app
roximately 1.5-fold compared with normal saline in severed mesenteric arter
ies of rats. Continuous infusion of TMPZ (1 mug/g per min) for 10 minutes a
lso significantly increased the bleeding time approximately 1.6-fold, and t
he bleeding time returned to baseline within 60 minutes after cessation of
TMPZ infusion. On the other hand. platelet thrombi formation was induced by
irradiation of mesenteric venules with filtered light in mice pretreated i
ntravenously with fluorescein sodium (10 mug/kg). When it was intravenously
injected, TMPZ (250 mug/g) significantly prolonged the latent period of th
e induction of platelet plug formation in mesenteric venules. TMPZ (250 mug
/g) prolonged occlusion time approximately 1.4-fold (183 +/- 18 seconds) co
mpared with that of normal saline (132 +/- 14 seconds). Furthermore. aspiri
n (300 mug/g) showed similar activity in the prolongation of occlusion time
in this experiment. In conclusion, these results suggest that TMPZ has eff
ective antithrombotic activity in vivo and may be a potential therapeutic a
gent for arterial thrombosis but must be assessed further for toxicity. (C)
2001 The Japanese Society of Hematology.