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Sphingomyelin phosphodiesterase 1 acid lysosomal (SMPD1; ASM)

Mouse and cell culture studies suggest inhibiting SMPD1 could be useful for treating depression. In human neuronal cell lines and in mice, the antidepressants amitriptyline and fluoxetine decreased SMPD1 activity and ceramide levels compared with vehicle. In a mouse model for stress-induced depression, the SMPD1 inhibitor fendiline decreased depression-like behaviors with potency comparable to that of antidepressant drugs. Next steps include identifying potent, selective inhibitors of SMPD1 and characterizing their effects in mouse models for depression.
Eli Lilly and Co. markets Prozac fluoxetine to treat major depressive disorder, obsessive-compulsive disorder (OCD), bulimia nervosa and panic disorder.
Amitriptyline is a generic antidepressant.
Fendiline is a research reagent (see Depressing sphingolipids, page 5).

SciBX 6(27); doi:10.1038/scibx.2013.690
Published online July 18, 2013

Unpatented; licensing status not applicable

Gulbins, E. et al. Nat. Med.; published online June 16, 2013;
Contact: Erich Gulbins, University of Duisburg-Essen, Essen, Germany
Contact: Johannes Kornhuber, University of Erlangen-Nuremberg,
Erlangen, Germany