THERAPY DOSSIER · th-656402f9c459

Acid sphingomyelinase inhibition (desipramine), plus genetic, small interfering RNA and antibody blockade of ASM/ceramide secretion

Drug · Desipramine (tricyclic antidepressant; norepinephrine reuptake/transporter inhibitor) used here as a functional acid sphingomyelinase (ASM) inhibitor.

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This record is classified as “NO TRAUMA TRANSLATION”. Read the indication and notes below for the specific context.

Evidence & regulatory context

Mechanism: Desipramine (tricyclic antidepressant; norepinephrine reuptake/transporter inhibitor) used here as a functional acid sphingomyelinase (ASM) inhibitor.
Target: Norepinephrine transporter (CHEMBL222)
Injury models: Radiation
Reported indication: Not recorded
First approval: 1964
Development stage: Not recorded
ChEMBL record: CHEMBL72 ↗
ChEMBL max phase: 4 / 4 (development scale, not regulatory approval)
Synonyms: Norpramin; Pertofrane; N-desmethylimipramine
Note: Not recorded

Clinical trials 2

0 linked trials carry an injury-indication flag. These flags support record-level exploration and sit alongside the stringent aggregate counts described in Methods.

NCT00366652 ↗PHASE3completed

Effects of DVS SR and Duloxetine on the Pharmacokinetics of Desipramine

Depression · Depressive Disorder

Enrolment: 20 · Results not recorded

NCT00990691 ↗PHASE2completed

Desipramine on Neurovegetative Parameters in Rett Syndrome

Rett Syndrome

Enrolment: 36 · Results not recorded

Preclinical evidence 1

1 studies reported at therapy level; 1 evidence entries itemised.

PMID 32291318 ↗2020Reported benefit

Secretion of Acid Sphingomyelinase and Ceramide by Endothelial Cells Contributes to Radiation-Induced Intestinal Toxicity.

MouseRadiationWild-type and acid sphingomyelinase knockout (ASMKO) miceMale

Model: Total body or abdominal irradiation at 15 Gy inducing gastrointestinal syndrome; supported by primary endothelial cell and intestinal T84 cell co-culture and enteroid models

Blocking endothelial secretion of acid sphingomyelinase or ceramide, genetically, pharmacologically or immunologically, abolished radiosensitisation of intestinal epithelial cells; ASMKO mice did not show the serum ceramide rise and did not develop intestinal failure injury. Ceramide reduced entero…

Extraction: extract · Supplied extraction confidence: 0.6. Machine-extracted fields require source verification.

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