Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The understanding of the properties of adrenergic receptors and modification of ring and the N-alkyl side chain constituents have resulted in adrenergic agents with a high degree of specificity for the lung and few cardiac and central nervous system stimulating problems. These agents are useful by aerosol and oral routes, alone and in addition to theophylline for asthma. Theophylline, which acts to increase cyclic AMP by inhibition of phosphodiesterase and beta 2 adrenergic agents which increase cyclic AMP by stimulating adenylate cyclase, are the mainstays of asthma therapy. Therapy is usually begun with theophylline. Persistent symptoms with adequate theophylline levels (10-20 mug/ml) indicates the need for a beta 2 adrenergic agent by aerosol or orally as a supplement. Occasional patients will not tolerate theophylline in any preparation and can be treated with beta 2 adrenergic agents with success. The future holds great promise for improved and safer beta 2 adrenergic agents which will offer the physician a more effective means of treating asthma.
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PMID:Treatment of asthma with theophylline and beta adrenergic agents. 1 64

Bronchial obstruction is mainly treated by bronchospasmolytics. They have different sites of action and work either by stimulating the beta-adrenergic receptors (beta-sympathicomimetics), by inhibiting the phosphodiesterase (theophylline-derivatives) or by blocking the cholinergic receptors (anticholinergica). Beta-sympathicomimetics do not only act via the beta-receptors but also by inhibiting the degranulation of the mast cells and thus preventing the liberation of spasmogenic substances. A very promising development is ipratropium bromide, an anticholinergic with a spasmolytic effect as pronounced as that of a beta2-adrenergic substance but with hardly any adverse side-effect. Glucocorticoids which are highly effective in bronchial asthma were shown to have also an "permissive effect" towards beta-sympathicomimetics.
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PMID:[New developments in the field of bronchospasmolytics]. 3 84

The contents of histamine and cyclic nucleotides were studied in leukocytes before and after a bronchoprovocation test on patients with extrinsic asthma. The bronchospastic response correlated significantly with the reduction of the amount of histamine in leukocytes isolated after the provocation. The leukocytes cyclic AMP and cyclic GMP contents were slightly reduced after the provocation, while the plasma level of cyclic AMP was markedly increased. The beta-adrenoceptor response was tested on leukocytes, before the provocation. A normal elevation of the cyclic AMP content was obtained when the leukocytes were stimulated with isoprenaline, but after the provocation, isoprenaline had no significant effect. Only when a phosphodiesterase inhibitor was present did isoprenaline increase the cyclic AMP level in the postprovocation tests. It is suggested that the mediator release from the immunologic target cells is of importance for the bronchospastic response and that a desensitization of the beta-adrenoceptors of these cells is evident after bronchoprovocation.
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PMID:Changes in histamine and cyclic nucleotide levels after bronchoprovocation in patients with extrinsic asthma. 8 5

Of the 22 patients with extrinsic bronchial asthma, 13 patients developed post-exercise bronchoconstriction after treadmill exercise, whereas in 9 patients treadmill exercise had no effect on the ventilatory capacity. No statistical difference in the resting lung volumes and CO transfer factor was found between the two groups. A significant inhibition of postexercise bronchoconstriction was observed in 12 of 13 patients following thymoxamine or cromolyn sodium inhalation. Inhibition of postexercise bronchoconstriction by alpha blockade with thymoxamine suggests that increased alpha adrenergic activity in the presence of diminished beta receptor responsiveness to catecholamines, norepinephrine released during exercise could have a marked alpha agonistic effect giving rise to bronchoconstriction. It has been suggested that cromolyn sodium has a cyclic phosphodiesterase inhibiting action. This might increase levels of AMP and restore the beta receptor responsiveness to catecholamines.
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PMID:The effect of thymoxamine and cromolyn sodium on postexercise bronchoconstriction in asthma. 13 Nov 39

Disodium cromoglycate (DSCG) prevents allergic asthma by inhibiting the release of chemical mediators of immediate-type allergic reactions. The mechanism of this action is unclear and prompted us to examine the effect of DSCG on cyclic adenosine 3',5'-monophosphate (cAMP), the implicated regulator of IgE-mediated reactions. We used the peripheral blood lymphocyte as a model to mirror the biochemical events occurring in the allergic shock organs. Isolated peripheral blood lymphocytes from perennial allergic asthmatic children receiving only DSCG had significantly (p less than 0.005) lower phosphodiesterase (PDE) activity (mean 1.05 +/- 0.17 SE per 10(6) cells) than normal individuals (2.93 +/- 0.14) and allergic children receiving methylxanthines (4.08 +/- 0.28) or no medications (3.58 +/- 0.2). DSCG (10 mug/ml) significantly lowered PDE activity in normal lymphocytes (p less than 0.005) in a beef heart extract (p less than 0.001), and 100 mug/ml lowered PDE activity in fetal rabbit lung homogenates (p less than 0.001). DSCG (10 mug/ml) significantly elevated (p less than 0.01) cAMP concentration in normal human lymphocytes (118 +/- 38 vs 30 +/- 10 picomoles cAMP/10(6) lymphocytes). Thus, DSCG appears to inhibit chemical mediator release by increasing intracellular cAMP through the inhibition of cAMP PDE.
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PMID:An action of disodium cromoglycate: inhibition of cyclic 3',5'-AMP phosphodiesterase. 17 50

Oral adrenergic substances (e.g., ephedrine) and phosphodiesterase inhibitors (e.g., theophylline) can have a prophylactic effect on natural or experimentally induced asthma by maintaining high levels of cyclic AMP in the target organ cells. This controlled, double-blind study evaluates these drugs alone and in a standard dosage combination in blocking asthma induced by the inhalation of pollen allergens among highly selected patients. The results support the claim that oral adrenergic drugs and xanthines can be useful in the prophylaxis of asthma.
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PMID:Pharmacologic modification of induced asthma. 17 26

Changes in cyclic-3', 5'-nucleotide phosphodiesterase activity of the peripheral blood leukocytes were investigated in patients with bronchial asthma. Leukocyte phosphodiesterase activity was significantly elevated during asthmatic attacks. Elevated activity was seen in most active asthmatics irrespective of the drug treatment. The ratio of the adenyl cyclase activity to the phosphodiesterase activity of the same leukocyte decreased to less than 1.0 during asthmatic attacks.
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PMID:Leukocyte cyclic-3', 5'-nucleotide phosphodiesterase activity in human bronchial asthma. 18 72

Activity of cAMP phosphodiesterase was similar in leukocytes of healthy persons and of the patients with bronchial asthma in the period of remission. The enzymatic activity was independent on the form of the impairment (infectious-allergic or atopic types). Sensivity of cAMP phosphodiesterase to the effect of its inhibitors and stimulants--theophylline, papaverine and imidazole was higher in the patients as compared with the healthy persons. Prolonged therapy with the phosphodiesterase inhibitors did not lead to development of resistance.
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PMID:[cAMP phosphodiesterase activity in the leukocytes in bronchial asthma]. 22 97

New therapeutic approaches to asthma involve either improvements in existing classes of drug, or the development of novel drugs. Over the last 20 years there have been no new types of drug introduced, although several new classes of compound are now under development. Improvements in existing bronchodilators include long-acting inhaled beta 2-agonists, methyl xanthines with a reduced side effect profile and M3-selective anticholinergics. New bronchodilators include K+ channel activators and selective phosphodiesterase inhibitors. Corticosteroids are the most effective anti-inflammatory drugs and there are attempts to develop inhaled steroids with greater topical potency or increased systemic metabolism, or to develop drugs which retain the anti-inflammatory effects of steroids without side effects. Steroids are probably effective in asthma by inhibiting the synthesis of cytokines and drugs which inhibit cytokine synthesis or receptors are now being sought. Inhibitors of mediator synthesis and receptors currently under development and leukotriene D4-antagonists are promising. Immunomodulatory drugs such as methotrexate, cyclosporin A and gold may be useful in more severe asthma, but drugs which modulate the immune abberation of asthma more specifically may be of more widespread use in the future. There is no immediate prospect of a cure for asthma and a drug which may be taken orally once daily and has no side effects would be ideal.
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PMID:Asthma. New therapeutic approaches. 135 69

Several new drugs are now under development for the treatment of asthma, either as improvements to existing classes of therapy or as novel agents. Amongst bronchodilators, long-acting inhaled beta 2-agonists (salmeterol and formoterol) look very promising and there is also interest in selective phosphodiesterase inhibitors, K+ channel-openers and nitrodilators. There are several new inhaled corticosteroids under development and more selective agents include leukotriene antagonists, 5-lipoxygenase inhibitors, bradykinin and tachykinin antagonists and immunomodulators. In the future, adhesion molecule inhibitors and cytokine inhibitors may be developed.
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PMID:New drugs for asthma. 135 72


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