LYSOSOMAL ALTERATIONS IN CULTURED MACROPHAGES EXPOSED TO ANOREXIGENIC AND PSYCHOTROPIC-DRUGS

  • 1 January 1976
    • journal article
    • research article
    • Vol. 35  (2) , 116-123
Abstract
Cultured rat macrophages were used for an in vitro study of drug-induced lipidosis. Cells were exposed for 24 h to equimolar concentrations (5 .times. 10-5 and 1 .times. 10-4 M) of the following amphiphilic (amphipathic) cationic drugs: chlorphentermine, amitriptyline, 1-chloro-amitriptyline, iprindole, noxiptiline, chlorpromazine. In addition, the less amphiphilic drug phentermine was used. Ultrastructurally, the cytologic changes essentially consisted of formation of multilamellated cytoplasmic inclusions, which possessed acid phosphatase activity. The abnormal inclusions are interpreted to result from intralysosomal accumulation of polar lipids. Under the present in vitro conditions all drugs except phentermine had similar potencies to induce such lysosomal alterations, in contrast to the great quantitative differences previously observed under in vivo conditions. The present results lend further support to a concept that regards a pronounced amphiphilic (amphipathic) character to be responsible for the lipidosis-inducing action of various cationic compounds. Cultured macrophages are suggested as a useful tool to investigate this structure-activity relationship, which under in vivo conditions may be obscured by superimposed parameters such as drug metabolism.