Agranulocytosis Induced by Certain Phenothiazine Derivatives

Phenothiazine derivatives implicated as a frequent cause of agranulocytosis include chlorpromazine, mepazine, promazine, and thioridazine. Perphenazine, prochlorperazine, and triflupromazine are also suspect, but not incriminated. Apparently promethazine and methdilazine do not cause agranulocytosis. Clinical and hematologic characteristics of phenothiazine-induced agranulocytosis suggest that the mechanisms underlying the development of this condition are related to a possible suppressive effect of phenothiazines on cell division. This suggests that even before exposure to chlorpromazine, sensitive patients have a less efficient mechanism for cell division or deoxyribonucleic acid synthesis than the nonsensitive ("normal") patients. Because of its in vitro affinity for soluble protein, it is possible that chlorpromazine exerts its effect by combining with biologically active proteins to inactivate their physiologic properties. Unexpected hematologic reactions may develop in rare cases from the administration of certain drugs in dosages that ordinarily are not harmful to most people. These reactions may result from the interaction of a