tiacrilast and Hypersensitivity

Increasing evidence suggests that neuropeptides may be important stimuli for mast cell secretion. Neuropeptide-induced histamine secretion from rat mast cells was inhibited by a variety of clinical and experimental antiallergic agents. The profile of responsiveness to this panel of drugs exhibited by peritoneal (PMC) and intestinal mucosal mast cells (IMC) was similar to that previously reported when histamine release was immunologically induced. Thus, cromoglycate, theophylline and Ro 22-3747 inhibited peptide-induced secretion from PMC but not from IMC. In contrast, doxantrazole was effective against PMC and IMC. Differences between IMC and PMC could not be attributed to the IMC isolation procedure. The results confirm the heterogeneity of responsiveness to antiallergic drugs exhibited by these mast cell subpopulations and indicate that it is not limited to immunologically induced secretion but also occurs when a neuropeptide is the secretory stimulus.

Topics: Animals; Cromolyn Sodium; Dose-Response Relationship, Drug; Histamine Release; Hypersensitivity; Intestinal Mucosa; Male; Mast Cells; Nerve Tissue Proteins; Peritoneal Cavity; Quinazolines; Rats; Rats, Inbred Strains; Theophylline; Thioxanthenes; Xanthones

A series of substituted (E)-3-(4-oxo-4H-quinazolin-3-yl)-2-propenoic acids was prepared and evaluated in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. Alkoxy, alkylthio, and isopropyl substituents at the 6- or 8-positions provided highly potent compounds. Conversion to the Z isomer, reduction of the side chain double bond, or reduction of the quinazoline ring resulted in substantial loss of activity. Among the analogues that exhibited oral activity in the PCA test, (E)-3-[6-(methylthio)-4-oxo-4H-quinazolin-3-yl]-2-propenoic acid (5i) was the most potent.

Topics: Animals; Hypersensitivity; Passive Cutaneous Anaphylaxis; Quinazolines; Rats; Structure-Activity Relationship