Inhibition by cinnarizine of the properdin-dependent activation of complement

Cinnarizine (1-benzhydryl-4-cinnamylpiperazine dihydrochloride), a well-known antagonist of vasoactive agents, has previously been shown to inhibit the activation of complement at the level of the fourth component. Cinnarizine was now tested in a system of complement activation by the properdin-dependent alternative pathway. At the concentration of 7.10(-5) M the compound completely inhibited the hemolytic reaction, which is the consequence of human complement activation in the presence of inulin or zymosan. This in vitro effect of cinnarizine was abolished by the addition of 1 mM MgCl2. These findings extend the anticomplementary activity of cinnarizine to the properdin pathway and support its interaction with the magnesium-dependent steps of the activation sequence.