ANTI-ALLERGIC PROPERTIES OF SQ 13,847, AN ORALLY EFFECTIVE AGENT .2. ACTIVITY INVITRO

  • 1 January 1980
    • journal article
    • research article
    • Vol. 213  (3) , 437-440
Abstract
SQ 13,847, a pyrazolo[1,5-c]quinazoline with potent oral antiallergic activity in the rat, was compared with its principal oxidative metabolite, SQ 12,903 [5,6-dihydro-5-oxopyrazolo[1,5-c]quinazoline-2-carboxylic acid], for ability to block the release of histamine from the rat mast cell in vitro. SQ 12,903, at concentrations in the range of 0.3-3 .mu.M, produced 50% inhibition of histamine release reactions triggered by dextran, antirat immunoglobulin (Ig) E or polymyxin B, but SQ 13,847 concentrations of 100 .mu.M or greater were required to produce equivalent inhibitory effects. The greater potency of SQ 12,903 relative to that of SQ 13,847, both in vitro and in passive cutaneous anaphylaxis via the i.v. route, and the structural similarity of SQ 12,903 to other antiallergic agents indicate that SQ 13,847 is a prodrug, requiring oxidation to SQ 12,903 for expression of maximum antiallergic activity. SQ 12,903, disodium cromoglycate and doxantrazole displayed similar time-dependent inhibition and cross-tachyphylaxis; apparently all 3 antiallergic agents block mast cell degranulation via a common mechanism.