BENZALKONIUM CHLORIDE - SELECTIVE INHIBITOR OF HISTAMINE-RELEASE INDUCED BY COMPOUND 48-80 AND OTHER POLYAMINES

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  • 1 January 1979
    • journal article
    • research article
    • Vol. 211  (3) , 711-715
Abstract
Benzalkonium chloride (BAC) is a mixture of quaternary benzyldimethylalkylammonium chlorides which inhibits histamine release induced by polyamines (48/80 [4-methoxy-N-methylbenzene ethanamine formaldehyde products], ATP, bradykinin, curare, guanethidine, polylysine, polymyxin B, polyTHIQ [polymerized-7-methoxytetrahydroisoquinoline] protamine, stilbamidine or substance P), but not that caused by antigens, concanavalin A, dextran, ionophores (A2318 [2-[(3.beta.,9.alpha.,11.beta.-trimethyl)-8-12-pyrrole carboxymethyl)-1,7-dioxaspiro[6.6]undecyl-2.beta.-methyl]-5-methyl aminobenzoxazol-4-carboxylic acid] or X-537A (lasalocid)), enzymes (chymotrypsin or phospholipase C), monoamines (dextromethorphan, meperidine or chlorpromazine) or detergents (decylamine, Triton X-100 [polyethylene glycol p-isoctylphenyl ether] or a fire ant venom alkylpiperidine). Inhibition by 1.5 and 3 .mu.g of BAC/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 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 .mu.g/ml. Heat inactivation (50.degree. C for 15 min) of the rat 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.