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Antiplatelet effect of a new inhibitor of thromboxane synthase and thromboxane A2 receptors.

Authors: E, Tubaro; L, Belogi; C M, Mezzadri;

Antiplatelet effect of a new inhibitor of thromboxane synthase and thromboxane A2 receptors.

Abstract

The effect on platelets of a new molecule denominated MED 27 (1-methyl-5-(4-methylbenzoyl)pyrrole-2-acetic acid 2-(theophylline-7-yl)ethyl ester, CAS 104333-87-1) was investigated. In vitro in the rat and using scalar doses of adenosine 5-diphosphate as challenge, the substance was found to be a platelet antiaggregating agent; in human platelets this effect was also found using stimuli such as epinephrine, collagen, arachidonic acid (AA), platelet aggregating factor (PAF) and U46619 (15-hydroxy-11 alpha,9 alpha-epoxymethanoprosta-5,13-dienoic acid). MED 27 ex vivo induced a dose-dependent inhibition of rat platelet aggregation at doses much lower than that of acetylsalicylic acid (ASA). Confirmation of the antiplatelet effect was obtained through in vitro human thromboxane B2(TXB2) synthase inhibition and MED 27 was very active compared with various non-steroidal anti-inflammatories (NSAIDs). These findings were confirmed in vivo in the rat: in this model MED 27 demonstrated dose-dependent and long-lasting activity. The drug was also found to be a TXA2 receptor antagonist and in this case also, the effect was dose-dependent and of long duration. In summary, MED 27 dually inhibits both thromboxane synthase and thromboxane receptors. It compares favourably with other NSAIDs of reference as an antiplatelet agent; this is also true when compared with ASA which, as opposed to MED 27, lacks any effect on TXA2 receptors.

Keywords

Blood Platelets, Male, Dose-Response Relationship, Drug, Platelet Aggregation, Receptors, Thromboxane, In Vitro Techniques, Dinoprostone, Rats, Rats, Sprague-Dawley, Thromboxane B2, Dogs, Theophylline, Animals, Humans, Female, Thromboxane-A Synthase, Enzyme Inhibitors, Rats, Wistar, Platelet Aggregation Inhibitors

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Powered by OpenAIRE graph
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
2
Average
Average
Average
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