Inhibition of Allergic Reactions by Cromoglycate and by a New Anti-Allergic Drug (10-Chloro-1,4,6,9-Tetrahydro-4,6-Dioxopyrido[3,2-g]Quinoline-2,8-Dicarboxylic Acid)

Self Cite

A new inhibitor of IgE-mediated allergic reactions has been studied in rats. This new inhibitor is chemically different from cromoglycate and shows qualitative and quantitative advantages over it. It is 2,500 times more active in rats than disodium cromoglycate and shows oral activity. This new inhibitor possesses no bronchodilator or end-organ antagonism activity and does not raise intracellular cAMP levels but as cromoglycate acts by inhibition of mediator release. Multiple high (25 mg/kg) doses in rats lead to tachyphylaxis. This effect is reversed both by decreasing the first dose and increasing the time between doses. Over a 5- to 10-fold concentration range, this inhibitor in mast cells can be stimulatory or inhibitory to ⁴⁵Ca⁺⁺ flux into cells. This ability to inhibit ionophore-induced ⁴⁵Ca⁺⁺ flux correlates well with inhibition of histamine release.

supporting

confidence: 80%

Inhibition of Allergic Reactions by Cromoglycate and by a New Anti-Allergy Drug U-42,585E

Hg¹,

Ca²,

Jb³

1978

Self Cite

“…Our finding that DSCG diminished the severity of the Ascaris-induced respiratory changes in the conscious monkey corrobor ates those of Johnson and Van Hout [2] and Patterson et al [7], who studied anesthe tized animals. Since the in vitro inhibiting action of DSCG in antigen-stimulated his tamine release in chopped monkey lung and bronchi has been documented [10], it sug gests the primary action of this agent, in the monkey, is attenuation of mast cell histam ine release.…”

Section: Discussionsupporting

confidence: 92%

Ascaris-Induced Respiratory Responses in the Conscious Rhesus Monkey

Weissberg¹,

Garay²

1979

Reproducible immediate-type respiratory responses were evoked in conscious monkeys, sensitive to inhaled Ascaris suum, for periods up to 18 months. These responses were characterized by decreases in tidal volume and increases in breathing rate that persisted for about 40 min. Maximum changes were seen 3–5 min after exposure to the aerosolized antigen and were often accompanied by coughing and increased movement of the animals within the plethysmograph used for monitoring their ventilatory changes. Significant inhibition of the Ascaris-induced respiratory changes were seen in animals treated with either isoproterenol or cromolyn sodium. However, the latter agent was not effective in reversing histamine-induced ventilatory changes. The conscious monkey appears to be a suitable animal for evaluating potential antiallergic drugs.

“…PRD-92-Ea inhibited the PCA reaction in the rat after oral administration but higher doses were required than those given intravenously. DSCG was completely inactive in the rat when given orally in doses up to 300 mg/kg and this finding agrees with the ex perience of others [9,17,18]. In the results to be published elsewhere [5] PRD-92-Ea exhibited tachyphylaxis in the rat PCA af ter intravenous predosing and cross-react ing tachyphylaxis after predosing with DSCG.…”

Section: Discussionsupporting

confidence: 91%

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

El-Azab¹,

Pb²

1977

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.