STRUCTURAL FEATURES OF THE QUINIDINE AND QUININE MOLECULES NECESSARY FOR BINDING OF DRUG-INDUCED ANTIBODIES TO HUMAN-PLATELETS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 104  (5) , 730-740
Abstract
Although most quinidine- and quinine-induced platelet antibodies react only in the presence of the drug that provoked sensitization, some are active with either quinidine or its stereoisomer, quinine; that is, they are cross-reactive. This suggests that the activity of drug-dependent antibodies is dependent on different structural features of the quinidine or quinine molecules. Reactions of 16 quinidine- and quinine-induced antibodies with quinidine, quinine and analogs of these drugs modified at the quinoline ring (desmethoxy-derivative), the quinuclidine ring (dihydro-derivative), or the asymmetric C(9)-hydroxyl position. It was found that the antibodies could be classified into 3 groups on the basis of their reactions with platelets in the presence of these compounds. Eight antibodies (group 1) reacted only in the presence of the sensitizing drug or its dihydro- or desmethoxy-derivative. Three antibodies (group 2) differed from those in group 1 only in that their reactions were markedly weakened when the primary desmethoxy-derivative was used. Five antibodies (group 3) reacted in the presence of the sensitizing drug, its stereoisomer and 1 or more of the analogs tested, including at least 1 of the C(9)-derivatives. Antibodies in this group gave stronger reactions with the sensitizing drug than with its stereoisomer. The heterogeneity among drug-induced platelet antibodies was confirmed by demonstrating that noncross-reactive antibodies (groups 1 and 2) are dependent for their activity on a specific configuration at the optically active C(9)-hydroxyl position. Some of these (group 2) also require the methoxy group for full reactivity. In contrast, cross-reactive antibodies (group 3) appear to be dependent on the quinoline ring common to all the analogs tested, but also require a specific configuration at C(9) for full reactivity. [The role of quinidine and quinine in drug-induced immunologic thrombocytopenia was outlined.].