New Inhibitor of Phosphodiesterase with Anti-bronchoconstrictor Properties

Davies, G. E.; Rose, F. L.; Ville, A. R. Somer

doi:10.1038/newbio234050a0

Cited by 21 publications

(3 citation statements)

References 3 publications

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“…In this leucocyte preparation, the potency of the new AH compounds was compared with that of a large number of compounds be longing to various groups of inhibitors. They included DSCG, /i-adrenoceptor stimulants (which seem to exert their effect through stimulation of adenyl cyclase), theophylline and other phosphodiesterase inhibitors, in cluding the new ICI derivatives, 30,966 and 58,301 [Davies et al, 1971] and dibutyryl cyclic adenosine 3',5'-phosphate (Calbiochem).…”

Section: Histamine Release From Leucocytesmentioning

confidence: 99%

Inhibition of Allergic Reactions by Cromoglycate and by a New Series of Compounds (AH 6556, AH 7079 and AH 7725)

Assem

1973

Int Arch Allergy Immunol

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(1) A new series of anti-allergic drugs (AH 6556, AH 7079 and AH 7725) were shown to inhibit immediate-type allergy. They act by inhibiting release of pharmacological mediators, and they do not possess any bronchodilator activity. (2) Inhibition of allergic reactions was shown experimentally in a wide range of in vitro test models, and supports the findings in the preliminary in vivo studies in experimental animals. (2) The experimental evidence suggests that these compounds have some qualitative and quantitative advantages over disodium cromoglycate.

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Section: Histamine Release From Leucocytesmentioning

confidence: 99%

Inhibition of Allergic Reactions by Cromoglycate and by a New Series of Compounds (AH 6556, AH 7079 and AH 7725)

Assem

1973

Int Arch Allergy Immunol

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“…Inhibition of cyclic nucleotide phosphodiesterase could elevate cellular cAMP levels. Compounds that inhibit the mammalian phosphodiesterase enzymes may possess important pharmacological activities such as elevation of fat cell lipolysis (3) and bronchodilation (4).…”

mentioning

confidence: 99%

Agar plate screening procedure for cyclic adenosine 3',5'-monophosphate and inhibitors of cyclic nucleotide phosphodiesterase

Somers¹,

Higgens²

1977

Appl Environ Microbiol

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A procedure is described for the semiquantitative measurement of cyclic adenosine 3',5'-monophosphate (cAMP) and detection of inhibitors of cAMP phosphodiesterase by an agar plate test. The assay organism was an adenyl cyclase-deficient mutant derived from Escherichia coli HfrH. In the presence of an acid base indicator, acid production from barbohydrate metabolism was observed as a yellow zone around filter paper disks containing cAMP. Since yellow zone formation reflects the presence of cAMP, a phosphodiesterase inhibitor can be detected indirectly by the presence of a yellow zone on assay plates from a reaction mixture of an inhibitor, phosphodiesterase, and cAMP. Three known cyclic nucleotide phosphodiesterase inhibitors were active against beef brain phosphodiesterase in this system.

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“…ICI 58,301 is not active in these conditions. Both compounds are potent inhibitors of 3':5'-cyclic AMP phosphodiesterase and it is speculated that this property is associated with their anti-anaphylactic ef fects.Research on the pharmacological properties of purine isosteres led to the discovery of two compounds which are potent inhibitors of bronchospasm in guinea pigs [6,8]. The compounds are: 3-acetamido-6-methyl-8-n-propyl-s-triazolo[4,3-a]pyrazine (ICI 58,301) [14,15] and 2-amino-6-methyl-5-oxo-4-n-propyl-4,5-dihydro-s-triazolo [l,5-a]pyrimidine (ICI 63,197) [9].…”

mentioning

confidence: 99%

Studies with Two New Phosphodiesterase Inhibitors (ICI 58,301 and ICI 63,197) on Anaphylaxis in Guinea Pigs, Mice and Rats

Davies¹,

Evans²

1973

Int Arch Allergy Immunol

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Two compounds, ICI 58,301 (3-acetamido-6-methyl-8-n-propyl-s-triazolo[4,3-a]pyrazine) and ICI 63,197 (2-amino-6-methyl-5-oxo-4-n-propyl-4,5,-dihydro-s-triazolo[l,5-a]pyrimidine) facilitate the recovery of guinea pigs which have been subjected to anaphylactic shock. ICI 63,197 also reduces the amount of histamine released from the isolated lungs of sensitized guinea pigs after injection of antigen, partially inhibits passive cutaneous anaphylaxis in guinea pigs, protects mice from anaphylactic shock, and inhibits passive cutaneous anaphylaxis in rats sensitized with homologous reaginic or heterologous antisera. ICI 58,301 is not active in these conditions. Both compounds are potent inhibitors of 3′:5′-cyclic AMP phosphodiesterase and it is speculated that this property is associated with their anti-anaphylactic effects.

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New Inhibitor of Phosphodiesterase with Anti-bronchoconstrictor Properties

Cited by 21 publications

References 3 publications

Inhibition of Allergic Reactions by Cromoglycate and by a New Series of Compounds (AH 6556, AH 7079 and AH 7725)

Inhibition of Allergic Reactions by Cromoglycate and by a New Series of Compounds (AH 6556, AH 7079 and AH 7725)

Agar plate screening procedure for cyclic adenosine 3',5'-monophosphate and inhibitors of cyclic nucleotide phosphodiesterase

Studies with Two New Phosphodiesterase Inhibitors (ICI 58,301 and ICI 63,197) on Anaphylaxis in Guinea Pigs, Mice and Rats

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