&lt;i&gt;In vitro&lt;/i&gt; Antagonism of the Mediators of Allergy by a Benzopyrano-Benzopyran Carboxylic Acid PR-D-92-EA

Possanza, G. J.; A, Bauen; Stewart, Paul

doi:10.1159/000231463

Cited by 9 publications

(7 citation statements)

References 3 publications

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“…The coronary spasm may contribute to the electrocardiographic abnormalities associated frequently with anaphylaxis in man and animals (Criep, 1931;Booth & Patterson, 1970;Criep & Woehler, 1971;Capurro & Levi, 1975 Compound PRD-92-EA is an agent that has marked anti-allergic properties (Stewart, Devlin & Freter, 1974) which are associated with inhibition of mast cell degranulation and a broad spectrum of receptor blocking activity towards agonists which include histamine, 5-HT and carbachol (Possanza, Bauen & Stewart, 1974, 1975Chand & Eyre, 1976;Holroyde & Eyre, 1977). Compound PRD-92 inhibited anaphylactic contraction of the coronary artery virtually completely.…”

Section: Discussionmentioning

confidence: 99%

CORONARY ANAPHYLAXIS in vitro

Chand

Eyre

1979

British J Pharmacology

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The reactivity of isolated coronary arteries and cardiac veins of the calf to selected chemical mediators of anaphylaxis and to sensitizing antigen (horse plasma) was studied. Both the coronary arteries and cardiac veins contracted to bradykinin, 5‐hydroxytryptamine (5‐HT), prostaglandin E2 (PGE2), PGF2α, histamine and carbachol. Isoprenaline and PGE1 relaxed vessels which had been partially contracted by PGF2α, PGE2, histamine, 5‐HT, bradykinin, carbachol or antigen. Horse plasma (antigen) contracted coronary vessels obtained from sensitized calves, but not from control calves. Subsequent antigen ‘challenge’ produced ‘desensitization’ (tachyphylaxis). After 1 or 2 h of rest, the anaphylactic response partially recovered although there was no change in tissue reactivity to the exogenous agonists. Specific doses of atropine, mepyramine (H1‐blocker) and methysergide (5‐HT antagonist) did not modify the anaphylactic reaction in coronary arteries, suggesting a negligible role for these biogenic amines. Compound PRD‐92‐EA (a new anti‐allergic agent) exhibited non‐specific receptor blocking activity towards histamine, 5‐HT and carbachol and inhibited the coronary anaphylactic reaction.

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Section: Discussionmentioning

confidence: 99%

CORONARY ANAPHYLAXIS in vitro

Chand

Eyre

1979

British J Pharmacology

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“…This effect has been documented by Possanza et al [16]. Apart from its action on mast cells and the antagonistic effect against some of the allergic mediators, PRD-92-Ea was almost devoid of any other pharmacological effect.…”

Section: Monkey 'Asthma' Modelmentioning

confidence: 53%

“…Against SRS-A and the prostaglandins E2 and Fit» PRD-92-Ea was much more potent and showed many of the features of a competitive antagonist [16].…”

Section: Discussionmentioning

confidence: 95%

“…DSCG has no antagonistic activity against the mediators of allergy which are released from mast cells, while in contrast PRD-92-Ea was shown to have a broad antagonistic profile [16], The activity against histamine, bradykinin and serotonin was probably too weak to be of much practical importance. However, in contrast to the classical antagonists against these mediators PRD-92-Ea was strikingly non toxic and its action readily reversible so that the isolated muscle strips tolerated ex tremely high concentrations of PRD-92-Ea and remained responsive for many hours.…”

Section: Discussionmentioning

confidence: 95%

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Pharmacologic Profile of a New Antiallergic Compound PRD-92-Ea

El-Azab¹,

Pb²

1977

Int Arch Allergy Immunol

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PRD-92-Ea [5,5-Dimethyl-11-oxo-5H, HH-(2) benzopyrano (4,3-g) (1) benzopyran-9-carboxylic acid ethanolamine], was an active antiallergic compound in rat and monkey experimental models of immediate hypersensitivity. It inhibited, in a dose-dependent manner, the rat PCA reaction after both intravenous and oral administration. It also inhibited the degranulation of rat peritoneal mast cells after antigenic challenge. PRD-92-Ea was also active in preventing bronchoconstriction in Ascaris-sensitive Rhesus monkeys after intravenous, topical and oral administration. Using chopped monkey tissues, it was found that PRD-92-Ea prevented histamine release from the respiratory mast cells, but not from the cutaneous mast cells. No reason for this dichotomy of effect is known. PRD-92-Ea showed antagonistic activity against the allergic mediators released from mast cells. In order of decreasing potency it was active against SRS-A (monkey lung), PGF_2α, PGE₂, serotonin, bradykinin and histamine. Apart from its antiallergic effects PRD-92-Ea had no other significant pharmacological activity.

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“…This com pound has the additional property of being well absorbed following oral administration in rat and monkey [4,5,10] and in man [6]. On the basis of in vitro studies, it has been reported that Ea is an antagonist of several putative mediators of asthma and in flammation [8], indicating that this com pound may be grouped with other anti allergy drugs having a mixed antagonist/anti allergy action, e.g. ketotifen [7,11] and oxatomide [2].…”

Section: Introductionmentioning

confidence: 99%

Anti-Allergy Properties of PRD-92 E<sub>a</sub> in Guinea Pig and Rat

Beets¹,

Meade²,

Morley³

1980

Int Arch Allergy Immunol

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The effects of PRD-92 Ea were examined on the increased plasma protein extravasation in the skin of guinea pig and rat elicited by specific antigens and spasmogenic mediators. PRD-92 Ea was found to be a potent inhibitor of rat PCA reactions when administered intradermally, intravenously or orally. This compound did not antagonize the local inflammatory responses of histamine, bradykinin or 5HT. This implies that in vivo PRD-92 Ea acts predominantly as an anti-allergy agent rather than a spasmogen antagonist. At high concentrations PRD-92 Ea directly increased vascular permeability when injected intradermally (> 250 μg/site) or administered by aerosol into the lung (> 10%). The importance of investigating such direct irritant actions of similar new drugs is discussed.

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<i>In vitro</i> Antagonism of the Mediators of Allergy by a Benzopyrano-Benzopyran Carboxylic Acid PR-D-92-EA

Cited by 9 publications

References 3 publications

CORONARY ANAPHYLAXIS in vitro

CORONARY ANAPHYLAXIS in vitro

Pharmacologic Profile of a New Antiallergic Compound PRD-92-Ea

Anti-Allergy Properties of PRD-92 E<sub>a</sub> in Guinea Pig and Rat

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