Benzalkonium chloride: selective inhibitor of histamine release induced by compound 48/80 and other polyamines.
Benzalkonium chloride (BAC) is a mixture of quaternary benzyldimethylalkylammonium chlorides which was found to inhibit histamine release induced by polyamines (48/80, ATP, bradykinin, curare, guanethidine, polylysine, polymyxin B, poly-THIQ, protamine, stilbamidine or substance P), but not that caused by antigens, concanavalin A, dextran, lonophores (A23187 or X-537A), enzymes (chymotrypsin or phospholipase C), monoamines (dextromethorphan, meperidine or chlorpromazine) or detergents (decylamine, Triton X-100 or a fire ant venom alkylpiperidine). Inhibition by 1.5 and 3 microgram of BAC per ml caused parallel shifts of the 48/80 dose-response curves to the right with no loss of efficacy, indicating that the antagonism was surmountable. Phospholipase C was partially inhibited by BAC, but Triton X-100 also inhibited phospholipase C (but not 48/80), indicating that the inhibition of phospholipase C by BAC was probably a nonspecific, detergent effect. BAC caused histamine release by itself at concentrations over 5 microgram/ml. Heat inactivation (50 degrees C for 15 min) of the mast cells did not prevent this release, suggesting a lytic mechanism for this action. Structure-activity relations studies on various members of the BAC family for their ability to inhibit 48/80-induced histamine release indicated that benzyldimethyltridecylammonium chloride was the most potent.
D000818:Animals; D001548:Benzalkonium Compounds / Q000494:pharmacology*; D005260:Female; D006636:Histamine Release / Q000187:drug effects*; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D011073:Polyamines / Q000037:antagonists & inhibitors*; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D010738:Type C Phospholipases / Q000494:pharmacology; D003189:p-Methoxy-N-methylphenethylamine / Q000037:antagonists & inhibitors*
D001548:Benzalkonium Compounds; D011073:Polyamines; D011092:Polyethylene Glycols; D003189:p-Methoxy-N-methylphenethylamine; D010738:Type C Phospholipases