Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C18H22N2.C2HF3O2 |
| Molecular Weight | 380.404 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
OC(=O)C(F)(F)F.CNCCCN1C2=CC=CC=C2CCC3=CC=CC=C13
InChI
InChIKey=UFQHEQUKRIFMOM-UHFFFAOYSA-N
InChI=1S/C18H22N2.C2HF3O2/c1-19-13-6-14-20-17-9-4-2-7-15(17)11-12-16-8-3-5-10-18(16)20;3-2(4,5)1(6)7/h2-5,7-10,19H,6,11-14H2,1H3;(H,6,7)
| 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 |
| Molecular Formula | C2HF3O2 |
| Molecular Weight | 114.0233 |
| 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 |
|---|---|---|---|
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] | ||||
| 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 |
|---|---|---|
| Ascending catecholamine pathways and amphetamine-induced locomotor activity: importance of dopamine and apparent non-involvement of norepinephrine. | 1975 Aug 15 |
|
| Repeated administration of desmethylimipramine blocks the reserpine-induced increase in tyrosine hydroxylase mRNA in locus coeruleus neurons of the rat. | 1991 Jul |
|
| Regulation of serotonin type 2 (5-HT2) and beta-adrenergic receptors in rat cerebral cortex following novel and classical antidepressant treatment. | 1991 Nov |
|
| Desipramine-induced oral-pharyngeal disturbances: stuttering and jaw myoclonus. | 1992 Dec |
|
| 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 |
|
| Desipramine in opioid-dependent cocaine abusers maintained on buprenorphine vs methadone. | 1999 Sep |
|
| National Patterns of Medication Treatment for Depression, 1987 to 2001. | 2001 Dec |
|
| Tricyclic antidepressants and the Brugada syndrome: an example of Brugada waves appearing after the administration of desipramine. | 2002 Aug |
|
| [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 |
|
| Utility of crossover designs in clinical trials: efficacy of desipramine vs. placebo in opioid-dependent cocaine abusers. | 2002 Spring |
|
| Comorbid major depressive disorder as a prognostic factor in cocaine-abusing buprenorphine-maintained patients treated with desipramine and contingency management. | 2003 Aug |
|
| 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 |
|
| Role of brain dopaminergic system in the adrenomedullin-induced diuresis and natriuresis. | 2003 Nov |
|
| Validation of a simple, ethologically relevant paradigm for assessing anxiety in mice. | 2003 Sep 1 |
|
| [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 |
|
| Discovering modes of action for therapeutic compounds using a genome-wide screen of yeast heterozygotes. | 2004 Jan 9 |
|
| 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 |
|
| Desipramine treatment for cocaine dependence in buprenorphine- or methadone-treated patients: baseline urine results as predictor of response. | 2005 Jan-Feb |
|
| 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 |
|
| 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 |
|
| [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 |
|
| 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 |
|
| The role of NMDA receptor antagonists in nicotine tolerance, sensitization, and physical dependence: a preclinical review. | 2008 Apr 30 |
|
| Comparison of the effects of desmethylimipramine on behavior in the forced swim test in peripubertal and adult rats. | 2008 Feb |
|
| Photophysics and photochemistry of imipramine, desimipramine, and clomipramine in several solvents: a fluorescence, 266 nm laser flash, and theoretical study. | 2008 Jan 10 |
|
| Narcolepsy: current treatment options and future approaches. | 2008 Jun |
|
| Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct rodent models of Parkinson's disease. | 2008 May 21 |
|
| Assessing the neuronal serotonergic target-based antidepressant stratagem: impact of in vivo interaction studies and knockout models. | 2008 Sep |
|
| Tetrabenazine as anti-chorea therapy in Huntington disease: an open-label continuation study. Huntington Study Group/TETRA-HD Investigators. | 2009 Dec 18 |
|
| 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 |
|
| 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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Edited
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| Record UNII |
5T6XJJ77M3
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| Record Status |
Validated (UNII)
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| Record Version |
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