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

Abstract

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.

A role for mast cells in adenosine A3 receptor‐mediated hypotension in the rat

“…The incomplete blockade of APNEA by sodium cromoglycate and lodoxamide remains to be explained. It is, however, entirely consistent with in vitro findings where mediator release inhibition is often incomplete and may show a bell-shaped doseresponse relationship (Johnson et al, 1978;Tanizaki et al, 1992). defining the role of the mast cell in a variety of experimental circumstances (see, for example, Di Rosa et al, 1971;Banks et al, 1990 the A3 receptor-mediated component of the response to AP-NEA, neither increased histamine levels per se nor modified the response to APNEA, mediator release can be unequivocally attributed to the effects of APNEA.…”

“…Since APNEA is relatively non-selective , the A3 receptor component of the cardiovascular response was effectively 'isolated' by pretreatment of animals with the broad spectrum adenosine receptor antagonist, 8-SPT, at a dose well in excess of those required to antagonize A1, A2A and A2B receptors in this preparation (Fozard & Carruthers, 1993a,b; see also (Brogden et al, 1974;Johnson et al, 1978). Dose-dependent blockade of the response to APNEA by both com- pounds with lodoxamide being clearly the more potent would thus be consistent with a role for mast cells in the response to APNEA.…”

Activity of a Novel Hydroquinone Inhibitor of Leukotriene Synthesis (U-66,858) in the Rhesus Monkey <i>Ascaris</i> Reactor

“…Addi tional blockers of the respiratory response to Ascaris have been described [Johnson and Van Hout, 1976;Johnson et al, 1978Johnson et al, , 1979, Recently, a prostacyclin analog, U-60,257 Piriprost, was found to be a selec tive inhibitor of leukotriene C and D synthesis in vitro [Bach et al, 1982],…”

Effects of FPL 55712, ETYA and Aminophylline upon Ascaris-Induced Bronchoconstriction in Cynomolgus Monkeys

“…Ascaris antigen (AA) induced bronchoconstriction in monkeys has been useful for the determination of preclinical anti-asthmatic activity of investigational anti-allergic compounds [1][2][3][4], In these studies, bron choconstriction was measured in anesthetized, spon taneously breathing monkeys after inhalation of mists generated from AA solutions of predetermined con centrations.…”