Is lox healthy
Antirheumatic drugs: new therapeutic approach LOX / COX inhibition
The therapy of pain and inflammation in inflammatory rheumatic diseases is often carried out using selective and non-selective nonsteroidal anti-inflammatory drugs (NSAIDs), the principle of which is to suppress prostaglandin synthesis by inhibiting the enzyme cyclooxygenase (COX). However, this principle does not take into account the role of leukotrienes in inflammatory processes and their role in the development of the gastrointestinal side effects that occur with nonselective NSAIDs.
The risk of serious gastrointestinal side effects cannot be completely ruled out even through the use of selective COX-2 inhibitors. Therefore, interest is increasingly directed towards the second key enzyme in arachidonic acid metabolism, 5-lipoxygenase (5-LOX).
Leukotrienes damage the lining of the stomach
The 5-lipoxygenase catalyzes the conversion of arachidonic acid into leukotrienes. To the same extent as the prostaglandins, the leukotrienes are also mediators of inflammation. For example, leukotrienes mediate the activation of inflammatory cells such as granulocytes and macrophages and increase the production of proinflammatory cytokines. With regard to the gastrointestinal tolerance of NSAIDs and specific COX-2 inhibitors, however, it is decisive that under the influence of leukotrienes there is an adhesion of neutrophils in the postcapillary vessels of the mucosa, which is accompanied by additional vasoconstriction. Both effects ultimately lead to ischemic damage to the gastric mucosa.
Blockage of COX and LOX
With Licofelone (M-3000), the first representative of a new class of active ingredients is now in clinical development (phase III), with which it is possible to effectively block both key enzymes of the arachidonic acid metabolism. Licofelone blocks both cyclooxygenase and lipoxygenase so that there is no increase in leukotriene formation despite cyclooxygenase inhibition. The success of this mechanism of action has been demonstrated in previous clinical studies with M-3000, in which good gastrointestinal tolerance and an effectiveness comparable to non-steroidal anti-inflammatory drugs in the treatment of osteoarthritis could be observed. ck
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