The effects of a 5-lipoxygenase inhibitor on asthma induced by cold, dry air

Article Abstract:

Arachidonic acid is the grandfather of many compounds which play roles in the mediation of inflammation. Many of the compounds believed to be important in the bronchoconstriction and inflammation which occurs in asthma are synthesized through the metabolism of arachidonic acid by the enzyme 5-lipoxygenase. While these products have been demonstrated to induce attacks of asthma, attempts to prevent asthmatic attacks by inhibiting 5-lipoxygenase have been disappointing. This may be due at least in part to the failure of some enzyme inhibitors to achieve satisfactory blockade of enzymatic activity within the human body. For this reason, an attempt was made to evaluate a novel inhibitor of 5-lipoxygenase, A-64077, which has previously been shown to be effective at inhibiting 5-lipoxygenase activity in laboratory animals. The compound was experimentally evaluated in 13 asthmatic volunteers who induced bronchoconstriction by hyperventilating in cold, dry air. Prior to breathing the cold, dry air, the patients received either a placebo or a capsule of A-64077. The response of the patient was measured biochemically through the analysis of blood specimens taken before and after the drug treatment. The response was also monitored physiologically, by the period of cold exposure which is necessary to produce a specific change in the FEV1, the volume of air which can be forcibly expelled in one second. The results showed that treatment with A-64077 resulted in a 74 percent reduction in the 5-lipoxygenase activity which could be induced in the blood samples. The treatment also increased by almost half the amount of time in the cold necessary to produce a 10 percent reduction in FEV1. The results show that inhibition of 5-lipoxygenase can result in significant reductions in the asthmatic response induced by cold, dry air. (Consumer Summary produced by Reliance Medical Information, Inc.)

Arachidonic acid

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Leukotrienes in asthma and allergic rhinitis

Article Abstract:

Fifty years have elapsed since scientists first noticed that allergic reaction produced a physiologically active mixture called "slow-reacting substance of anaphylaxis". The chemical structure of the active substances was not worked out until the late 1970s, when these substances were termed leukotrienes. The leukotrienes play a myriad of roles in immune reactions, particularly in inflammatory reactions, asthma, and allergy. Two articles in the December 20, 1990 issue of The New England Journal of Medicine report on the demonstration that particular leukotrienes are important in asthma and allergic rhinitis. This demonstration was made possible by the development of a new experimental compound called A-64077. This substance specifically inhibits an enzyme, 5-lipoxygenase, which is critical in the metabolic pathway leading to the leukotrienes in question. In both studies, oral doses of A-64077 led to significant reductions in the asthmatic or the allergic response. However, it is too soon to assume that a new therapeutic treatment has been found. The leukotrienes have normal physiologic functions, as well as the pathologic functions so obvious in asthma. Both of these studies were very short-term and measured only immediate results. Researchers must be alert to the possibility that long-term use may affect other organ systems. The inhibition of cyclooxygenase, another enzyme involved in similar metabolic processes, has already been shown to lead to gastric ulceration and hypertension in some patients. Although the potential for inhibitors of 5-lipoxygenase, such as A-64077, seems exciting, much remains to be learned about the physiological function of the leukotrienes. (Consumer Summary produced by Reliance Medical Information, Inc.)

Allergy, Hay-fever, Hay fever, Respiratory allergy, Respiratory hypersensitivity

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Antileukotrienes in the treatment of asthma

Article Abstract:

A new class of drugs called antileukotrienes show promise in the treatment of asthma. Leukotrienes are produced in certain cells in the lungs, and have been shown to play an important role in the contraction of smooth muscle, which causes airway constriction in asthma patients. These drugs are particularly indicated for aspirin-induced asthma, having been shown to be completely effective in preventing this type of asthmatic response. Further study of antileukotriene treatment is needed to establish specific recommendations for treating asthmatic conditions.

Innovations, Drug therapy, Antiasthmatic agents

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