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=C(CCC3=C1C=CC=C3)C=CC=C2
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 Date-1.61395196E11 |
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 n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 Sources: |
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 n = 1 Health Status: unhealthy Age Group: adult Population Size: 1 Sources: |
|
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 Condition: major depressive disorde 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 n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 Sources: |
Hypotension | grade 5, 1 patient | 2500 mg single, oral Overdose |
healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 Sources: |
Seizures | grade 5, 1 patient | 2500 mg single, oral Overdose |
healthy, 2 years n = 1 Health Status: healthy Age Group: 2 years Sex: F Population Size: 1 Sources: |
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 Condition: major depressive disorde 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 |
---|---|---|
Desipramine-induced oral-pharyngeal disturbances: stuttering and jaw myoclonus. | 1992 Dec |
|
Control of depression with fluoxetine and antiseizure medication in a brain-injured patient. | 1992 Feb |
|
Oral contraceptives and panic disorder. | 1992 May |
|
Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone. | 1999 Sep |
|
Antidepressant drugs appear to enhance cocaine-induced toxicity. | 2000 Feb |
|
National Patterns of Medication Treatment for Depression, 1987 to 2001. | 2001 Dec |
|
Microheterogeneity of myocardial blood flow. | 2001 Nov |
|
[Effect of local and systemic desipramine administration on extracellular noradrenaline in the myocardium of rats]. | 2002 Dec |
|
Antidepressants reduce phosphoinositide-specific phospholipase C (PI-PLC) activity and the mRNA and protein expression of selective PLC beta 1 isozyme in rat brain. | 2002 Dec |
|
Acute treatment with the cyclic antidepressant desipramine, but not fluoxetine, increases membrane-associated G protein-coupled receptor kinases 2/3 in rat brain. | 2002 Dec |
|
Chronic inhibition of the norepinephrine transporter in the brain participates in seizure sensitization to cocaine and local anesthetics. | 2003 Feb 21 |
|
Desipramine and contingency management for cocaine and opiate dependence in buprenorphine maintained patients. | 2003 Jun 5 |
|
Validation of a simple, ethologically relevant paradigm for assessing anxiety in mice. | 2003 Sep 1 |
|
Ethnic differences in substance abuse treatment retention, compliance, and outcome from two clinical trials. | 2004 Feb |
|
Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes. | 2004 Jan 9 |
|
Evaluation of fresh and cryopreserved hepatocytes as in vitro drug metabolism tools for the prediction of metabolic clearance. | 2004 Nov |
|
Inhibition of G protein-activated inwardly rectifying K+ channels by various antidepressant drugs. | 2004 Oct |
|
Interferon-alpha-induced modulation of glucocorticoid and serotonin receptors as a mechanism of depression. | 2005 Jun |
|
Brugada syndrome precipitated by a tricyclic antidepressant. | 2005 May |
|
A selective test for antidepressant treatments using rats bred for stress-induced reduction of motor activity in the swim test. | 2005 Oct |
|
Enhanced neurally evoked responses and inhibition of norepinephrine reuptake in rat mesenteric arteries after spinal transection. | 2006 Jan |
|
[Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations]. | 2006 Jun |
|
Frequency of high-risk use of QT-prolonging medications. | 2006 Jun |
|
Rhesus monkey trace amine-associated receptor 1 signaling: enhancement by monoamine transporters and attenuation by the D2 autoreceptor in vitro. | 2007 Apr |
|
Reduced evoked fos expression in activity-related brain regions in animal models of behavioral depression. | 2007 Aug 15 |
|
Desipramine activated Bcl-2 expression and inhibited lipopolysaccharide-induced apoptosis in hippocampus-derived adult neural stem cells. | 2007 May |
|
Reduction of high-affinity beta2-adrenergic receptor binding by hyperforin and hyperoside on rat C6 glioblastoma cells measured by fluorescence correlation spectroscopy. | 2007 May 1 |
|
A possible role for the endocannabinoid system in the neurobiology of depression. | 2007 Nov 19 |
|
The role of the entorhinal cortex in extinction: influences of aging. | 2008 |
|
Do desipramine [10,11-dihydro-5-[3-(methylamino) propyl]-5H-dibenz[b,f]azepine monohydrochloride] and fluoxetine [N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-propan-1-amine] ameliorate the extent of colonic damage induced by acetic acid in rats? | 2008 Dec |
|
The 5-hydroxytryptamine2A receptor antagonist R-(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl-4-piperidinemethanol (M100907) attenuates impulsivity after both drug-induced disruption (dizocilpine) and enhancement (antidepressant drugs) of differential-reinforcement-of-low-rate 72-s behavior in the rat. | 2008 Dec |
|
A novel approach for predicting antidepressant-induced sexual dysfunction in rats. | 2008 Jan |
|
D-161, a novel pyran-based triple monoamine transporter blocker: behavioral pharmacological evidence for antidepressant-like action. | 2008 Jul 28 |
|
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies. | 2008 Nov 4 |
|
Association of changes in norepinephrine and serotonin transporter expression with the long-term behavioral effects of antidepressant drugs. | 2009 May |
|
MPTP-induced neuroblast apoptosis in the subventricular zone is not regulated by dopamine or other monoamine transporters. | 2009 Nov |
|
Time course and dose response of alpha tocopherol on oxidative stress in haemodialysis patients. | 2009 Oct 22 |
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
by
admin
on
Edited
Fri Dec 16 16:39:03 UTC 2022
by
admin
on
Fri Dec 16 16:39:03 UTC 2022
|
Record UNII |
TG537D343B
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Official Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Common Name | English |
Classification Tree | Code System | Code | ||
---|---|---|---|---|
|
NCI_THESAURUS |
C94727
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
||
|
NDF-RT |
N0000175752
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
||
|
LIVERTOX |
NBK548233
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
||
|
WHO-ATC |
N06AA01
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
||
|
WHO-VATC |
QN06AA01
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
50-47-5
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
CHEMBL72
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
DTXSID6022896
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
2995
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
SUB06995MIG
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
1500
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
47781
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
200-040-0
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
3052
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
812
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
3247
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | RxNorm | ||
|
DB01151
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
M4191
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | Merck Index | ||
|
2399
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
DESIPRAMINE
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
D003891
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
C61700
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
TG537D343B
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
TG537D343B
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY | |||
|
Desipramine
Created by
admin on Fri Dec 16 16:39:03 UTC 2022 , Edited by admin on Fri Dec 16 16:39:03 UTC 2022
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
TRANSPORTER -> INHIBITOR | |||
|
SALT/SOLVATE -> PARENT | |||
|
METABOLIC ENZYME -> SUBSTRATE |
Metabolizing reaction by CYP2D6: Hydroxylation
|
||
|
TRANSPORTER -> INHIBITOR | |||
|
TRANSPORTER -> INHIBITOR | |||
|
TRANSPORTER -> SUBSTRATE | |||
|
TARGET -> INHIBITOR | |||
|
METABOLIC ENZYME -> SUBSTRATE |
Pharmacological action: Tricyclic antidepressant drug (TCA)
|
||
|
BINDER->LIGAND |
|
||
|
TRANSPORTER -> INHIBITOR | |||
|
SALT/SOLVATE -> PARENT |
Related Record | Type | Details | ||
---|---|---|---|---|
|
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).
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
ACTIVE MOIETY |