New inhibitor of reagin-mediated anaphylaxis

Broughton, Barbara J.; Chaplen, P.; Knowles, P.; Lunt, E.; Pain, D. L.; Wooldridge, K. R. H.; Ford, R. E.; Marshall, Stuart; Walker, Joyce L.; Maxwell, D. R.

doi:10.1038/251650a0

Cited by 47 publications

(21 citation statements)

References 3 publications

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“…M&B 22948 is a derivative of methylxanthine and is another new inhibitor of reagin-mediated anaphylaxis (Broughton, Chaplen, Knowles, Lunt, Pain, Wooldridge, Ford, Marshall, Walker & Maxwell, 1974). The inhibition of the Schultz-Dale reaction by this compound may be due to the inhibition of formation and release of histamine and SRS-A (Broughton et al, 1974;Burka & Eyre, 1975) by virtue of blocking cyclic 3',5'-adenosine monophosphate phosphodiesterase.…”

Section: Discussionmentioning

confidence: 99%

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The Pharmacology of Anaphylaxis in the Chicken Intestine

Chand

Eyre

1976

British J Pharmacology

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Section: Discussionmentioning

confidence: 99%

“…The inhibition of the Schultz-Dale reaction by this compound may be due to the inhibition of formation and release of histamine and SRS-A (Broughton et al, 1974;Burka & Eyre, 1975) by virtue of blocking cyclic 3',5'-adenosine monophosphate phosphodiesterase.…”

Section: Discussionmentioning

confidence: 99%

The Pharmacology of Anaphylaxis in the Chicken Intestine

Chand

Eyre

1976

British J Pharmacology

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“…The role of cyclic AMP in modulating histamine and SRS-A release seems to be well established. M&B 22,948 is a derivative of methylxanthine [Broughton et al, 1974] and it is likely that this drug inhibits SRS-A'1 "' synthesis and release by increasing cyclic AMP levels by inhibiting phosphodiesterase. DECC also possibly possesses some anti-phosphodiesterase activity as there is known to be a marked synergistic effect between DECC and isoproterenol , Chlorphenesin, on the other hand, is believed to activate adenyl cy clase.…”

Section: Discussionmentioning

confidence: 99%

“…M&B 22,948 has recently been shown to inhibit reagin-mediated ana phylaxis in a number of test systems, including the release of histamine and SRS-A from human lung [Broughton et al, 1974].…”

Section: Introductionmentioning

confidence: 99%

Modulation of the Formation and Release of Bovine SRS-A <i>in vitro</i> by several Anti-Anaphylactic Drugs

Burka¹,

Eyre²

1975

Int Arch Allergy Immunol

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Abstract. Slow-reacting substance of anaphylaxis (SRS-A) is released immunologically from bovine lung in vitro. Various drugs known to protect calves and other animals during anaphylaxis were tested to investigate their modulation of the for mation and release of SRS-A. The anti-inflammatory drugs, meclofenamate and as pirin, potentiated SRS-A release. Chlorphenesin and diethylcarbamazine citrate at high concentrations both inhibited SRS-A release. Two new anti-anaphylactic drugs, PR-D-92-EA and M&B 22,948, were particularly effective in inhibiting SRS-A re lease at low concentrations. The possible modes of actions of these drugs are dis cussed.

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“…Its clinical effectiveness has been attributed to its activity as an inhibitor of IgE-mediated release of bronchospastic mediators from mast cells both in vitro and in vivo [12,16,27], Since DSCG is ineffective orally, the search has been con tinued for an orally effective inhibitor of mediator re lease. Several new inhibitors of mediator release have been discovered and are in various stages of develop ment [2,5,8,9,15,19,35,36]. Three widely used in vitro models for the discovery of new inhibitors of the immunologic and/or non-immunoiogic release of histamine are: (a) rat peritoneal mast cells, (b) guinea pig lung slices and (c) human basophils [9].…”

Section: Introductionmentioning

confidence: 99%

RHC 3024: Antiallergic Activity in vitro and Comparison with Disodium Cromoglycate and Other Antiallergic Agents

Khandwala¹,

Coutts²,

Dally-Meade³

et al. 1983

Int Arch Allergy Immunol

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Abstract. RHC 3024 has been investigated for its antiallergic activity in three in vitro models of anaphylaxis. We have also compared its activity profile in these models with that of disodium cromoglycate (DSCG) and other antiallergic agents. As an inhibitor of antigen-induced release of histamine from rat mast cells RHC 3024 was 4 times more potent than DSCG. In the same model the activity profile of RHC 3024 was identical to that of DSCG in the following respects: loss of inhibitory activity with increasing preincubation time, reversibility of the inhibition, tachyphylaxis and cross-tachyphylaxis to each other and inability to inhibit histamine release stimulated by Ca++ ionophore, dextran/phosphatidyl serine and compound 48/80. Both drugs had no effect in the other two models, IgG|-mediated histamine release from guinea pig lung and anti-IgE-induced histamine release from human basophils. We conclude: (1) RHC 3024 is a potent inhibitor of mediator release with a me chanism of action similar to that of DSCG, M&B 22,948, PRD-92-Ea and AH-7725 and (2) the in vitro activity profiles of proxicromil, doxantrazole, ICI 74,917 and WY-16,922 are different from DSCG and RHC 3024.

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New inhibitor of reagin-mediated anaphylaxis

Cited by 47 publications

References 3 publications

The Pharmacology of Anaphylaxis in the Chicken Intestine

The Pharmacology of Anaphylaxis in the Chicken Intestine

Modulation of the Formation and Release of Bovine SRS-A <i>in vitro</i> by several Anti-Anaphylactic Drugs

RHC 3024: Antiallergic Activity in vitro and Comparison with Disodium Cromoglycate and Other Antiallergic Agents

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