Functional Inhibitors of Acid Sphingomyelinase (FIASMAs): a novel pharmacological group of drugs with broad clinical applications

Cell Physiol Biochem. 2010;26(1):9-20. doi: 10.1159/000315101. Epub 2010 May 18.


Acid sphingomyelinase (ASM) is an important lipid-metabolizing enzyme cleaving sphingomyelin to ceramide, mainly within lysosomes. Acid ceramidase (AC) further degrades ceramide to sphingosine which can then be phosphorylated to sphingosine-1-phosphate. Ceramide and its metabolite sphingosine-1-phosphate have been shown to antagonistically regulate apoptosis, cellular differentiation, proliferation and cell migration. Inhibitors of ASM or AC therefore hold promise for a number of new clinical therapies, e.g. for Alzheimer's disease and major depression on the one hand and cancer on the other. Inhibitors of ASM have been known for a long time. Cationic amphiphilic substances induce the detachment of ASM protein from inner lysosomal membranes with its consecutive inactivation, thereby working as functional inhibitors of ASM. We recently experimentally identified a large number of hitherto unknown functional inhibitors of ASM and determined specific physicochemical properties of such cationic amphiphilic substances that functionally inhibit ASM. We propose the acronym "FIASMA" (Functional Inhibitor of Acid SphingoMyelinAse) for members of this large group of compounds with a broad range of new clinical indications. FIASMAs differ markedly with respect to molecular structure and current clinical indication. Most of the available FIASMAs are licensed for medical use in humans, are minimally toxic and may therefore be applied for disease states associated with increased activity of ASM.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acid Ceramidase / antagonists & inhibitors
  • Acid Ceramidase / metabolism
  • Alzheimer Disease / drug therapy
  • Clinical Trials as Topic
  • Desipramine / chemistry
  • Desipramine / pharmacokinetics
  • Desipramine / therapeutic use
  • Humans
  • Phosphodiesterase Inhibitors / chemistry*
  • Phosphodiesterase Inhibitors / pharmacokinetics
  • Phosphodiesterase Inhibitors / therapeutic use
  • Sphingomyelin Phosphodiesterase / antagonists & inhibitors*
  • Sphingomyelin Phosphodiesterase / metabolism


  • Phosphodiesterase Inhibitors
  • Sphingomyelin Phosphodiesterase
  • Acid Ceramidase
  • Desipramine