Substituted ammonium ions as allergenic determinants in drug allergy

Serious, and occasionally fatal, anaphylactic-like (anaphylactoid) reactions may occur when a patient is exposed to a drug for the first time. Apart from the penicillins, nothing is known of the nature of antigenic or sensitizing drug determinants and, as yet, there is no evidence for the involvement of IgE antibodies in most drug reactions. Muscle relaxants such as alcuronium have been implicated in many life-threatening anaphylactoid reactions but the mechanisms remain unclear. We have now investigated the possibility that drug-specific IgE antibodies are involved by using an alcuronium-carrier complex in a radioimmunoassay with patients' sera. Alcuronium-reactive antibodies were found in five drug-sensitive subjects and most of the antibodies cross-reacted with other muscle relaxants and with a variety of apparently structurally unrelated drugs. Structure-activity studies designed to explore the molecular basis of the antibody binding established that quaternary and tertiary ammonium ions were the complementary allergenic sites on the reactive drugs. These structures occur widely in many drugs but also in foods, cosmetics, disinfectants and industrial materials. Hence, there would seem to be ample opportunity for sensitive individuals to come into contact with and synthesize IgE antibodies to these unusual, and previously unsuspected, antigenic determinants.