Indomethacin antiplatelet effect

ML-3000 ((2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizine-5-yl)-acetic acid) is a nonantioxidant dual inhibitor of both cyclooxygenase and 5-lipoxygenase. ML-3000 has been compared to indomethacin in a number of experimental models of inflammation. The analgesic effects of ML-3000 have also been assessed in a number of animal models. Phase II studies have shown a wide range of activities, including anti-inflammatory, analgesic, antiplatelet and antiasthmatic properties (Laufer et al., 1994 Chin and Wallace, 1999). 

Preparations from plant materials containing salicylate have been used to treat pain and fever (Stone, 1763) from ancient times into the nineteenth century, when synthetic salicylic acid was synthesized in Germany and used for the same purposes. Acetyl salicylate, aspirin, synthesized as a prodrug for salicylate, was introduced by Bayer in 1899 (Dreser, 1899) and is still widely used to treat pain, fever, and inflammation. In low doses aspirin is also used by many to reduce the incidence of heart attacks by an antithrombotic effect (Antiplatelet Trialists Collaboration, 1994). Eventually, other drugs with therapeutic effects similar to those of aspirin were introduced, including indomethacin, ibuprofen, and naproxen. These... 

Reversible inhibitors of COX 1 and COX 2, with analgesic, antipyretic, and anti-inflammatory actions, include ibuprofen, naproxen, indomethacin, ketorolac, and sulindac. When used as antiinflammatory agents, they are usually no more effective than ASA, but they may be better tolerated. All have antiplatelet actions (reversible) at moderate (not low) doses and cause bleeding tendencies. 

The antiplatelet action of aspirin results from the fact that inhibition of thromboxane synthesis is essentially permanent in platelets they lack the machinery for new protein synthesis. In contrast, inhibition of prostacyclin synthesis in the vascular endothelium is temporary because these cells can synthesize new enzyme. Inhibition of prostaglandin synthesis also results in important anti-inflammatory effects. Inhibition of synthesis of fever-inducing prostaglandins in the brain produces the antipyretic action of NSAIDs. Closure of a patent ductus arteriosus in an otherwise normal infant can be accelerated with a potent NSAID such as indomethacin. 

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