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 |
---|---|---|
Low dose tricyclic tachycardia. | 1991 Jan |
|
Changes in convulsion susceptibility of lidocaine by alteration of brain catecholaminergic functions. | 1991 May |
|
Sudden self-harm while taking fluoxetine. | 1992 Aug |
|
Increased pulse and blood pressure associated with desipramine treatment of bulimia nervosa. | 1992 Jun |
|
Trazodone induction of migraine headache through mCPP. | 1992 May |
|
National Patterns of Medication Treatment for Depression, 1987 to 2001. | 2001 Dec |
|
Inhibition of cytochrome P450 enzymes participating in p-nitrophenol hydroxylation by drugs known as CYP2E1 inhibitors. | 2004 Apr 15 |
|
Chronic treatment with desipramine and fluoxetine modulate BDNF, CaMKKalpha and CaMKKbeta mRNA levels in the hippocampus of transgenic mice expressing antisense RNA against the glucocorticoid receptor. | 2004 Dec |
|
Ethnic differences in substance abuse treatment retention, compliance, and outcome from two clinical trials. | 2004 Feb |
|
Clinical implications of genetic polymorphism of CYP2D6 in Mexican Americans. | 2004 Jun 1 |
|
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 |
|
Brain-derived tumor necrosis factor-alpha and its involvement in noradrenergic neuron functioning involved in the mechanism of action of an antidepressant. | 2004 Sep |
|
Reboxetine for the treatment of patients with Cocaine Dependence Disorder. | 2005 Apr |
|
Blood pressure changes associated with medication treatment of adults with attention-deficit/hyperactivity disorder. | 2005 Feb |
|
Desipramine treatment for cocaine dependence in buprenorphine- or methadone-treated patients: baseline urine results as predictor of response. | 2005 Jan-Feb |
|
Coadministration of histone deacetylase inhibitors and perifosine synergistically induces apoptosis in human leukemia cells through Akt and ERK1/2 inactivation and the generation of ceramide and reactive oxygen species. | 2005 Mar 15 |
|
Selective cortical VGLUT1 increase as a marker for antidepressant activity. | 2005 Nov |
|
Interaction of organic cations with a newly identified plasma membrane monoamine transporter. | 2005 Nov |
|
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 |
|
The involvement of norepinephrine and microglia in hypothalamic and splenic IL-1beta responses to stress. | 2006 Apr |
|
Response to SSRI-induced enuresis: a case report. | 2006 Feb |
|
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 |
|
Down-regulation of norepinephrine transporter function induced by chronic administration of desipramine linking to the alteration of sensitivity of local-anesthetics-induced convulsions and the counteraction by co-administration with local anesthetics. | 2006 Jun 22 |
|
Pharmacokinetics of desipramine HCl when administered with cinacalcet HCl. | 2007 Feb |
|
The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review. | 2008 Apr 30 |
|
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 |
|
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 |
|
Narcolepsy: current treatment options and future approaches. | 2008 Jun |
|
Impaired parasympathetic function increases susceptibility to inflammatory bowel disease in a mouse model of depression. | 2008 Jun |
|
Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease. | 2008 May 21 |
|
Evaluation of the repeated open-space swim model of depression in the mouse. | 2008 Nov |
|
Community-based randomised controlled trial evaluating falls and osteoporosis risk management strategies. | 2008 Nov 4 |
|
Assessing the neuronal serotonergic target-based antidepressant stratagem: impact of in vivo interaction studies and knockout models. | 2008 Sep |
|
Neuronal damage and protection in the pathophysiology and treatment of psychiatric illness: stress and depression. | 2009 |
|
Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators. | 2009 Dec 18 |
|
Behavioral sensitization to cocaine: cooperation between glucocorticoids and epinephrine. | 2009 Jul |
|
Reactivation of inflammatory bowel disease in a mouse model of depression. | 2009 Jun |
|
Desipramine-induced Ca-independent apoptosis in Mg63 human osteosarcoma cells: dependence on P38 mitogen-activated protein kinase-regulated activation of caspase 3. | 2009 Mar |
|
Antidepressants influence somatostatin levels and receptor pharmacology in brain. | 2009 Mar |
|
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 |
|
Transient supersensitivity to alpha-adrenoceptor agonists, and distinct hyper-reactivity to vasopressin and angiotensin II after denervation of rat tail artery. | 2010 Jan |
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
Wed Jul 05 22:47:22 UTC 2023
by
admin
on
Wed Jul 05 22:47:22 UTC 2023
|
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 Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
||
|
NDF-RT |
N0000175752
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
||
|
LIVERTOX |
NBK548233
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
||
|
WHO-ATC |
N06AA01
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
||
|
WHO-VATC |
QN06AA01
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
50-47-5
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
CHEMBL72
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
DTXSID6022896
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
100000083169
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
2995
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
SUB06995MIG
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
1500
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
47781
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
200-040-0
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
3052
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
812
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
3247
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | RxNorm | ||
|
DB01151
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
M4191
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | Merck Index | ||
|
2399
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
DESIPRAMINE
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
D003891
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
C61700
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
TG537D343B
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
TG537D343B
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY | |||
|
Desipramine
Created by
admin on Wed Jul 05 22:47:22 UTC 2023 , Edited by admin on Wed Jul 05 22:47:22 UTC 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
SALT/SOLVATE -> PARENT | |||
|
TRANSPORTER -> SUBSTRATE | |||
|
METABOLIC ENZYME -> SUBSTRATE |
Metabolizing reaction by CYP2D6: Hydroxylation
|
||
|
TARGET -> INHIBITOR | |||
|
METABOLIC ENZYME -> SUBSTRATE |
Pharmacological action: Tricyclic antidepressant drug (TCA)
|
||
|
TRANSPORTER -> INHIBITOR | |||
|
BINDER->LIGAND |
|
||
|
TRANSPORTER -> INHIBITOR | |||
|
TRANSPORTER -> INHIBITOR | |||
|
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 |