Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons.
| Title: | Inhibition of acid sphingomyelinase by tricyclic antidepressants and analogons. |
|---|---|
| Authors: | Beckmann N; Department of Molecular Biology, Institute of Molecular Biology, University of Duisburg-Essen Essen, Germany.; Sharma D; Department of Molecular Biology, Institute of Molecular Biology, University of Duisburg-Essen Essen, Germany.; Gulbins E; Department of Molecular Biology, Institute of Molecular Biology, University of Duisburg-Essen Essen, Germany.; Becker KA; Department of Molecular Biology, Institute of Molecular Biology, University of Duisburg-Essen Essen, Germany.; Edelmann B; Department of Molecular Biology, Institute of Molecular Biology, University of Duisburg-Essen Essen, Germany. |
| Source: | Frontiers in physiology [Front Physiol] 2014 Sep 02; Vol. 5, pp. 331. Date of Electronic Publication: 2014 Sep 02 (Print Publication: 2014). |
| Publication Type: | Journal Article; Review |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation Country of Publication: Switzerland NLM ID: 101549006 Publication Model: eCollection Cited Medium: Print ISSN: 1664-042X (Print) Linking ISSN: 1664042X NLM ISO Abbreviation: Front Physiol Subsets: PubMed not MEDLINE |
| Imprint Name(s): | Original Publication: Lausanne : Frontiers Research Foundation |
| Abstract: | Amitriptyline, a tricyclic antidepressant, has been used in the clinic to treat a number of disorders, in particular major depression and neuropathic pain. In the 1970s the ability of tricyclic antidepressants to inhibit acid sphingomyelinase (ASM) was discovered. The enzyme ASM catalyzes the hydrolysis of sphingomyelin to ceramide. ASM and ceramide were shown to play a crucial role in a wide range of diseases, including cancer, cystic fibrosis, diabetes, Alzheimer's disease, and major depression, as well as viral (e.g., measles virus) and bacterial (e.g., Staphylococcus aureus, Pseudomonas aeruginosa) infections. Ceramide molecules may act in these diseases by the alteration of membrane biophysics, the self-association of ceramide molecules within the cell membrane and the ultimate formation of larger ceramide-enriched membrane domains/platforms. These domains were shown to serve the clustering of certain receptors such as CD95 and may also act in the above named diseases. The potential to block the generation of ceramide by inhibiting the ASM has opened up new therapeutic approaches for the treatment of these conditions. Since amitriptyline is one of the longest used clinical drugs and side effects are well studied, it could potentially become a cheap and easily accessible medication for patients suffering from these diseases. In this review, we aim to provide an overview of current in vitro and in vivo studies and clinical trials utilizing amitriptyline to inhibit ASM and contemplate possible future applications of the drug. |
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| Contributed Indexing: | Keywords: acid sphingomyelinase; amitriptyline; antidepressants; ceramide; signaling |
| Entry Date(s): | Date Created: 20140918 Date Completed: 20140917 Latest Revision: 20211021 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC4151525 |
| DOI: | 10.3389/fphys.2014.00331 |
| PMID: | 25228885 |
| Database: | MEDLINE |
Journal Article; Review