Leukotriene synthesis inhibitors

Dube LM, Swanson LJ, Awni W. Zileuton, a leukotriene synthesis inhibitor in the management of chronic asthma. Clinical pharmacokinetics and safety. Chn Rev AUergy Immunol 1999 17(1-2) 213-21. 

Leukotriene-synthesis inhibitors The formation of leukotrienes depends on lipoxygenation of arachidonic acid by 5-lipoxygenase. Zileuton is a potent and selective inhibitor of 5-lipoxygenase activity and thus inhibits the formation of all 5-lipoxygenase products. Thus, in addition to... 

In connection with the work on the relationship between chemical structure and anti-inflammatory activity, the effect of ursolic acid, betulin, betulinic acid and erythrodiol on a system of chronic dermal edema and cellular proliferation caused by repeated administration of TPA has recently been examined [89], This experimental model of chronic inflammation has considerable selectivity for corticosteroids and leukotriene synthesis inhibitors. Erythrodiol and ursolic acid were significantly effective and also reduced the neutrophil infiltration detected by MPO activity. The lupane derivatives, betulin and betulinic acid, despite their possible steroid-like mechanism of action [47], were not effective in the chronic model. This result could mean that a six-member E ring of the pentacyclic structure is necessary for the activity against a multiple dose of TPA. The data confirm that a hydroxyl group at the C-28 position is important for the activity, as is also true in the case of erythrodiol, and it may explain the anti-inflammatory effect of this compound in each of the methods. 

Leukotriene Receptor Antagonists and Leukotriene Synthesis Inhibitors... 

A drug that directly inhibits 5-lipoxygenase and reduces leukotriene synthesis Inhibitor of LTD receptors... 

A number of attempts to alter the course of ALI/ARDS pharmacologically have not been proven to be successful. These include the use of exogenous surfactant, glucocorticoids, antioxidant (n-acetylcysteine), prostaglandin and leukotriene synthesis inhibitors (hetoconazole, ibuprofen), prostaglandin El, inhaled nitric oxide, and pentoxifylline (159,160). Trials with antibodies aimed at blocking inflammation provoked by endotoxin, TNF-a, and IL-1 have also not been proven to be successful... 

Zembowicz A, Mastalerz L, Setkowicz M, Radzis-zewski W, Szczeklik A Safety of cyclooxygenase-2 inhibitors and increased leukotriene synthesis in chronic idiopathic urticaria with sensitivity to nonsteroidal anti-inflammatory drugs. Arch Dermatol 2003 139 1577-1582. 

Holgate ST, Bradding P, Sampson AP. Leukotriene antagonists and synthesis inhibitors new directions in asthma therapy. J Allergy Clin Immunol 1996 98 1-13. 

Zileuton (Zyflo) is an inhibitor of leukotriene synthesis. The dose of zileuton tablets is 600 mg four times daily with meals and at bedtime. The recommended dose of zileuton extended-release tablets is two 600-mg tablets twice daily, within 1 hour after morning and evening meals (total daily dose 2,400 mg). 

Leukotriene inhibitors, one leukotriene inhibitor blocks leukotriene synthesis by inhibiting the action of 5-lipooxygenase (Zileuton Zyflo). Another blocks leukotriene receptors on the surface of smooth-muscle cells and eosinophils (Montelukast Singulair). 

A number of other types of drug are under development. These include agents that interfere with leukotriene synthesis (see LIPOXYGENASE inhibitors), interleukin-1 antagonists, monoclonal antibodies linked to cytotoxic drugs etc. See also IMMUNOMODULATORS. 

For the reasons given above, agents that interfere with leukotriene synthesis or actions, are of great interest in relation to limiting inflammatory reactions. The sites amenable to pharmacological manipulation include (I) the upstream inhibition of arachidonic acid production from phospholipids (which is a rate-limiting step see PHOSPHOLIPASE inhibitors) (2) the inactivation of five-... 

Leukotriene (LK) Leukotriene is the primary bronchoconstrictor. This increases migration of eosinophil, increases mucous production and increases edema in the bronchi, resulting in bronchoconstriction. There are two types of leukotriene modifiers LT receptor antagonists and LT synthesis inhibitors. Both reduce inflammatory symptoms of asthma. Leukotriene modifiers include ... 

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