Details
Stereochemistry | ACHIRAL |
Molecular Formula | C18H22N2 |
Molecular Weight | 266.3807 |
Optical Activity | NONE |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
CNCCCN1C2=CC=CC=C2CCC3=CC=CC=C13
InChI
InChIKey=HCYAFALTSJYZDH-UHFFFAOYSA-N
InChI=1S/C18H22N2/c1-19-13-6-14-20-17-9-4-2-7-15(17)11-12-16-8-3-5-10-18(16)20/h2-5,7-10,19H,6,11-14H2,1H3
Molecular Formula | C18H22N2 |
Molecular Weight | 266.3807 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 0 |
Optical Activity | NONE |
Desipramine is a tricyclic antidepressant that was approved by the FDA in 1964. It was derived from imipramine, which was the first tricyclic antidepressant to be manufactured. Desipramine is one of many tricyclic antidepressants, and this type of antidepressant gets its name due to its three-ring chemical structure. Desipramine, a secondary amine tricyclic antidepressant, is structurally related to both the skeletal muscle relaxant cyclobenzaprine and the thioxanthene antipsychotics such as thiothixene. It is the active metabolite of imipramine, a tertiary amine TCA. The acute effects of desipramine include inhibition of noradrenaline re-uptake at noradrenergic nerve endings and inhibition of serotonin (5-hydroxy tryptamine, 5HT) re-uptake at the serotoninergic nerve endings in the central nervous system. Desipramine exhibits greater noradrenergic re-uptake inhibition compared to the tertiary amine TCA imipramine. In addition to inhibiting neurotransmitter re-uptake, desipramine down-regulates beta-adrenergic receptors in the cerebral cortex and sensitizes serotonergic receptors with chronic use. The overall effect is increased serotonergic transmission. Antidepressant effects are typically observed 2 - 4 weeks following the onset of therapy though some patients may require up to 8 weeks of therapy prior to symptom improvement. Patients experiencing more severe depressive episodes may respond quicker than those with mild depressive symptoms. Desipramine is marketed under the trade name Norpramin, indicated for the treatment of depression.
CNS Activity
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL222 |
1.5 nM [IC50] | ||
163.0 nM [Ki] | |||
Target ID: CHEMBL224 Sources: https://www.drugbank.ca/drugs/DB01151 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | NORPRAMIN Approved UseDesipramine hydrochloride tablets are indicated for the treatment of depression. Launch Date1964 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
21.8 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16680561 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESIPRAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
656 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16680561 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESIPRAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/16680561 |
50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered: |
DESIPRAMINE plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.78% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/4386616 |
DESIPRAMINE plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse events |
---|---|---|
2500 mg single, oral Overdose |
healthy, 2 years |
Other AEs: Coma, Seizures... Other AEs: Coma (grade 5, 1 patient) Sources: Seizures (grade 5, 1 patient) Hypotension (grade 5, 1 patient) |
300 mg 1 times / day multiple, oral Highest studied dose Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: |
unhealthy, adult |
|
25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: |
unhealthy, children | adolescents | and young adults Health Status: unhealthy Age Group: children | adolescents | and young adults Sources: |
Other AEs: Suicidal ideation... Other AEs: Suicidal ideation Sources: |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Coma | grade 5, 1 patient | 2500 mg single, oral Overdose |
healthy, 2 years |
Hypotension | grade 5, 1 patient | 2500 mg single, oral Overdose |
healthy, 2 years |
Seizures | grade 5, 1 patient | 2500 mg single, oral Overdose |
healthy, 2 years |
Suicidal ideation | 25 mg 1 times / day multiple, oral Recommended Dose: 25 mg, 1 times / day Route: oral Route: multiple Dose: 25 mg, 1 times / day Sources: |
unhealthy, children | adolescents | and young adults Health Status: unhealthy Age Group: children | adolescents | and young adults Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes [IC50 16 uM] | ||||
yes [Inhibition 20 uM] | ||||
yes [Inhibition 20 uM] | ||||
yes [Inhibition 20 uM] | ||||
yes [Inhibition 20 uM] | ||||
yes [Ki 14 uM] | ||||
Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1381398/pdf/brjclinpharm00042-0080.pdf#page=2 Page: 2.0 |
yes [Ki 2.3 uM] | |||
yes [Ki 283 uM] | ||||
yes [Ki 55.7 uM] |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
yes | no (co-administration study) Comment: Ketoconazole did not alter the pharmacokinetics of orally administered desipramine in healthy volunteers; Genetic deficiency in CYP2D6 activity results in a 85% lower oral clearance of desipramine, as shown by a single dose pharmacokinetic study in healthy volunteers Sources: https://pubmed.ncbi.nlm.nih.gov/9758674/ |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
Sources: https://pubmed.ncbi.nlm.nih.gov/21120454/ Page: 11.0 |
PubMed
Title | Date | PubMed |
---|---|---|
Reversal of desipramine toxicity in rats using drug-specific antibody Fab' fragment: effects on hypotension and interaction with sodium bicarbonate. | 1992 Mar |
|
Oral contraceptives and panic disorder. | 1992 May |
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Effect of IAP and chronic antidepressant administration on the 5HT1A receptor in rat cortical membranes. | 1992 May |
|
Effect of tolcapone on the haemodynamic effects and tolerability of desipramine. | 2000 |
|
Antidepressant drugs appear to enhance cocaine-induced toxicity. | 2000 Feb |
|
Prediction of treatment outcome by baseline urine cocaine results and self-reported cocaine use for cocaine and opioid dependence. | 2003 |
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Antidepressant drug treatment induces Arc gene expression in the rat brain. | 2003 |
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Comorbid major depressive disorder as a prognostic factor in cocaine-abusing buprenorphine-maintained patients treated with desipramine and contingency management. | 2003 Aug |
|
Selective cortical VGLUT1 increase as a marker for antidepressant activity. | 2005 Nov |
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Desipramine treatment of cocaine-dependent patients with depression: a placebo-controlled trial. | 2005 Nov 1 |
|
A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test. | 2005 Oct |
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The effects of desmethylimipramine on cyclic AMP-stimulated gene transcription in a model cell system. | 2005 Sep 1 |
|
The role of the entorhinal cortex in extinction: influences of aging. | 2008 |
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Desipramine-induced apoptosis in human PC3 prostate cancer cells: activation of JNK kinase and caspase-3 pathways and a protective role of [Ca2+]i elevation. | 2008 Aug 19 |
|
D-161, a novel pyran-based triple monoamine transporter blocker: behavioral pharmacological evidence for antidepressant-like action. | 2008 Jul 28 |
|
Desipramine potentiation of the acute depressant effects of ethanol: modulation by alpha2-adrenoreceptors and stress. | 2008 Oct |
|
Desipramine-induced Ca-independent apoptosis in Mg63 human osteosarcoma cells: dependence on P38 mitogen-activated protein kinase-regulated activation of caspase 3. | 2009 Mar |
|
Association of changes in norepinephrine and serotonin transporter expression with the long-term behavioral effects of antidepressant drugs. | 2009 May |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/desipramine.html
Usual Adult Dose for Depression
100 to 200 mg orally per day
Maximum dose: 300 mg orally per day
Comments:
-Dosage should be initiated at a lower level and increased according to tolerance and clinical response.
-In severely ill patients, dosage may be further increased to 300 mg per day if needed.
-Treatment of patients requiring as much as 300 mg should generally be initiated in hospitals.
Usual Geriatric Dose for Depression
25 to 100 mg orally per day
Maximum dose: 150 mg orally per day
Route of Administration:
Oral
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12388651
Neuronal uptake 1 inhibitor desipramine (100 nM) decreased NE in 60-min hypothermic ischemia in isolated perfused guinea pig hearts.
Substance Class |
Chemical
Created
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admin
on
Edited
Mon Mar 31 17:52:13 GMT 2025
by
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on
Mon Mar 31 17:52:13 GMT 2025
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Record UNII |
TG537D343B
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Record Status |
Validated (UNII)
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Record Version |
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C94727
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NDF-RT |
N0000175752
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LIVERTOX |
NBK548233
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WHO-ATC |
N06AA01
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WHO-VATC |
QN06AA01
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50-47-5
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CHEMBL72
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DTXSID6022896
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100000083169
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2995
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SUB06995MIG
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1500
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47781
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200-040-0
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3052
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3247
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DB01151
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m4191
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2399
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DESIPRAMINE
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D003891
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C61700
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TG537D343B
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TG537D343B
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Desipramine
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE |
Metabolizing reaction by CYP2D6: Hydroxylation
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TARGET -> INHIBITOR |
BINDING
IC50
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TRANSPORTER -> INHIBITOR | |||
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TARGET -> INHIBITOR | |||
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METABOLIC ENZYME -> SUBSTRATE |
Pharmacological action: Tricyclic antidepressant drug (TCA)
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BINDER->LIGAND |
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TRANSPORTER -> SUBSTRATE | |||
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TRANSPORTER -> INHIBITOR | |||
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TRANSPORTER -> INHIBITOR | |||
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SALT/SOLVATE -> PARENT |
Related Record | Type | Details | ||
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PARENT -> METABOLITE ACTIVE |
Imipramine has activities at both the serotonin and norepeinephrine transporters with greater affinity for the serotonin transporter while desipramine and 2-hydroxydesipramine have greater affinities for the norepinephrine transporter (Owens et al., 1997).
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Related Record | Type | Details | ||
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PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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