Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C18H22N2 |
| Molecular Weight | 266.3813 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CNCCCN1c2ccccc2CCc3ccccc31
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 | 266.3813 |
| 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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL222 |
1.5 nM [IC50] | ||
| 163.0 nM [Ki] | |||
Target ID: CHEMBL224 |
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 |
|---|---|---|---|
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] | ||||
| 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 |
Tox targets
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
Page: 11.0 |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Low dose desipramine treatment of cocaine-related panic attacks. | 1991 Dec |
|
| Changes in convulsion susceptibility of lidocaine by alteration of brain catecholaminergic functions. | 1991 May |
|
| Increased pulse and blood pressure associated with desipramine treatment of bulimia nervosa. | 1992 Jun |
|
| Oral contraceptives and panic disorder. | 1992 May |
|
| Bupropion-induced carbohydrate craving and weight gain. | 1992 Oct |
|
| National Patterns of Medication Treatment for Depression, 1987 to 2001. | 2001 Dec |
|
| [Effects of neurotensin microinjected into ventral tegmental area on spontaneous motor activity in neonatal 6-hydroxydopamine-treated rats]. | 2004 Apr |
|
| 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 |
|
| NO induced apoptosis of vascular smooth muscle cells accompanied by ceramide increase. | 2004 May |
|
| Norepinephrine-deficient mice lack responses to antidepressant drugs, including selective serotonin reuptake inhibitors. | 2004 May 25 |
|
| 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 |
|
| Brugada syndrome precipitated by a tricyclic antidepressant. | 2005 May |
|
| 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 effects of desmethylimipramine on cyclic AMP-stimulated gene transcription in a model cell system. | 2005 Sep 1 |
|
| Nigrostriatal damage with 6-OHDA: validation of routinely applied procedures. | 2006 Aug |
|
| 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 |
|
| Anti-inflammatory properties of desipramine and fluoxetine. | 2007 May 3 |
|
| CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment. | 2007 May 9 |
|
| 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 |
|
| 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 |
|
| 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 |
|
| Desipramine potentiation of the acute depressant effects of ethanol: modulation by alpha2-adrenoreceptors and stress. | 2008 Oct |
|
| 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
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
| Substance Class |
Chemical
Created
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Sat Jun 26 12:09:22 UTC 2021
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Sat Jun 26 12:09:22 UTC 2021
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| Record UNII |
TG537D343B
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| Record Status |
Validated (UNII)
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NCI_THESAURUS |
C94727
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NDF-RT |
N0000175752
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LIVERTOX |
283
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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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50-47-5
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2995
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SUB06995MIG
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1500
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200-040-0
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3052
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812
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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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Desipramine
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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TRANSPORTER -> SUBSTRATE | |||
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|
SALT/SOLVATE -> PARENT | |||
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TRANSPORTER -> INHIBITOR | |||
|
METABOLIC ENZYME -> SUBSTRATE |
Metabolizing reaction by CYP2D6: Hydroxylation
|
||
|
TRANSPORTER -> INHIBITOR | |||
|
|
TARGET -> INHIBITOR | |||
|
TRANSPORTER -> INHIBITOR | |||
|
METABOLIC ENZYME -> SUBSTRATE |
Pharmacological action: Tricyclic antidepressant drug (TCA)
|
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|
BINDER->LIGAND |
|
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|
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
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| Related Record | Type | Details | ||
|---|---|---|---|---|
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ACTIVE MOIETY |
