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 action of a new antiallergic agent, 10-(3-quinuclidinylmethyl) phenothiazine or LM 209, on cAMP phosphodiesterase (PDE) was studied on a guinea-pig lung preparation and compared with that of other compounds such as cromoglycate (I), dexamethasone (II), dexchlorpheniramine (III), promethazine (IV) and theophylline (V). Compounds I, IV and V are competitive inhibitors whereas LM 209 and compound III are non competitive inhibitors of PDE. Compound II is practically inactive on the enzyme. Compounds III and V produce an inhibition of equal intensity, independently of the substrate concentration. Compounds I and IV are more active on PDE with low affinity than on PDE with strong affinity, whereas it is the contrary with LM 209. The mechanism of action of LM 209 at the pulmonary level is discussed in the light of these findings.
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PMID:[Inhibition of 3', 5'-cyclic AMP phosphodiesterase in the guinea pig lung by a new anti-allergic: 10-(3-quinuclidinylmethyl) phenothiazine (LM 209)]. 17 83

The antiallergic effects of 10-(3-quinuclidinylmethyl)phenothiazine (mequitazine) were investigated in vitro. The results obtained were as follows: 1) In the isolated trachea and lung parenchyma of guinea pigs, mequitazine showed a fairly potent antagonistic action against contractions induced by both histamine (Hi) and acetylcholine (ACh). Mequitazine was much less potent in antihistaminic action and slightly more potent in anticholinergic action than ketotifen. The contractions of the preparation by leukotriene (LT) D4 were antagonized by mequitazine, although the potency was moderate, showing an IC50 value of 2.3 x 10(-5) g/ml in the trachea and 5.1 x 10(-5)g/ml in the lung parenchyma. Mequitazine had no effect on the contraction of the trachea by PGF2 alpha, but inhibited that of the lung parenchyma with pA2 = 7.0. 2) Mequitazine (10(-6) g/ml) slightly inhibited the Schultz-Dale reaction of the isolated guinea pig trachea, while ketotifen at the same concentration did not show any effect. 3) The contraction of the isolated guinea pig trachea by Ca2+ influx was slightly inhibited by mequitazine (10(-5) g/ml). 4) Mequitazine competitively inhibited the cyclic AMP-dependent phosphodiesterase activity from the rat lung with a potency of 10 times and 5 times more than those of ketotifen and theophylline, respectively. 5) Mequitazine (10(-6) to 10(-5) M) suppressed both the anaphylactic and phospholipase A2-induced histamine release from the peritoneal cells of rats. 6) Mequitazine (10(-5) g/ml) also inhibited the anaphylactic and Ca ionophore-induced histamine release from the leukocytes of the atopic patients and normal subjects. 7) The anaphylactic releases of histamine, LTB4 and peptide LT from the human lung fragments were dose-dependently inhibited by mequitazine (10(-7) approximately 10(-5) g/ml).
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PMID:[Antiallergic effects of mequitazine. 1. In vitro experiments]. 246 60