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Arzneimittel-Forschung 1986-Dec

Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 5th communication: antiplatelet effect of the drug and antiinflammatory effect of its main metabolite.

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K Tsurumi
K Kyuki
M Yanagihara
J Hasegawa
H Fujimura

Ključne riječi

Sažetak

Since nonsteroidal antiinflammatory drugs (NSAID) usually have an antiplatelet effect, the inhibitory effect of 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl) propionic acid (CN-100), which exerts a potent antiinflammatory effect, was compared with those of reference drugs, indometacin and pranoprofen, in this study. Indometacin at 10(-5) mol/l inhibited completely (100%) rat and rabbit platelet aggregation induced by collagen and arachidonic acid. Pranoprofen at 10(-5) mol/l also entirely inhibited rat platelet aggregation induced by the two aggregators, but an about 10 times higher concentration was required to produce 100% inhibition of rabbit platelet aggregation. CN-100 at 10(-5) mol/l exerted 100% inhibition of rat platelet aggregation induced by collagen, whereas more than 10(-4) mol/l was needed to exhibit 100% inhibition of aggregation induced by arachidonic acid and ADP. The inhibitory activity of CN-100 on aggregation of rat platelets ex vivo was weaker than those of reference NSAID, i.e., the antiplatelet effect of CN-100 was found to be weak. The main metabolite of CN-100 also had a weak antiplatelet effect, and its antiinflammatory effect on carrageenin edema and UV erythema was apparently weaker than that of CN-100. The inhibitory effect of the metabolite on endotoxin diarrhea was weak. The ulcerogenic effect of the metabolite on gastric mucosa was similar to that of CN-100, but the effect rarely seemed to be a clinical problem because it was basically weak.

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