lodoxamide-tromethamine and Hypersensitivity

Lodoxamide tromethamine and several other anti-allergy drugs, i.e. inhibitors of rat passive cutaneous anaphylaxis, are inhibitors of purified xanthine oxidase. Inhibition is noncompetitive with Ki's in the 1-13 micromolar range. Lodoxamide tromethamine had no effect on another flavoprotein, glucose oxidase. Other studies have shown several of these drugs are inhibitors of aldose reductase. It is speculated that the anti-allergy drugs inhibit mediator release from mast cells by blocking univalent electron transfers which are essential for release.

Topics: Aldehyde Reductase; Amino Acids; Drug Evaluation, Preclinical; Histamine H1 Antagonists; Hypersensitivity; Kinetics; Mast Cells; Nitriles; Oxamic Acid; Tromethamine; Xanthine Oxidase

The antiallergy drugs, cromolyn sodium and lodoxamide tromethamine (U-42,585E) show in vitro dose responses which are bell-shaped or biphasic in mast cells. The nature of the biphasic dose response is poorly understood; however, through the use of specific antagonists, it has been possible to show that at the high concentrations of these drugs leading to enhanced histamine release or multiple high-dose tachyphylaxis, a cholinergic receptor is stimulated in the cell. This receptor is muscarinic in nature and can be blocked by atropine or quinuclidinyl benzilate (QNB). Prevention of multiple dose tachyphylaxis to either drug can be modulated by pretreatment with atropine or QNB. High concentrations of both drugs cause the cell accumulation of cyclic-guanosine monophosphate through stimulation of guanyl cyclase and prevention of cGMP breakdown by inhibition of the phosphodiesterase (PDE) for cGMP.

Topics: Animals; Atropine; Cromolyn Sodium; Cyclic AMP; Dose-Response Relationship, Drug; Histamine Release; Hypersensitivity; Nitriles; Oxamic Acid; p-Methoxy-N-methylphenethylamine; Phenylenediamines; Phosphoric Diester Hydrolases; Quinuclidinyl Benzilate; Rats; Receptors, Cholinergic; Receptors, Muscarinic; Time Factors; Tromethamine